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University of California San Francisco

QCRG

The QCRG AViDD Program

The QCRG (Quantitative Biosciences Institute Coronavirus Research Group) AViDD Program is an interdisciplinary program that aims to identify new direct-acting antivirals for SARS-CoV-2 and 19 other viruses. The project brings together a team of 45 investigators from 14 different institutions in this proposal with a history of collaboration; 31 of these have co-published together on 41 papers on SARS-CoV-2, efforts that have laid a strong foundation for the QCRG AViDD Program.

Initially, the QCRG will focus on eight target classes from eight viral families (Coronaviridae, Picornaviridae, Togaviridae, Flaviviridae, Hantaviridae, Arenaviridae, Nairoviridae and Paramyxoviridae), including seven coronaviruses, with a focus on SARS-CoV-2, where the viral RNA and 12 proteins will be targeted. In addition to the SARS-CoV-2 RNA (Project 1), these will include the Nsp3 PLP and Nsp5 Mpro proteases (Project 2); the Nsp3 macrodomain  (Project 5);  the RdRp polymerase, Nsp7, Nsp8 and Nsp12 (Project 2) the structural proteins E (Project 3), N (Project 6) and M (Projects 3 and 6); the methyltransferases Nsp10/14 and Nsp16 (Project 4); and the accessory protein involved in regulating immune response, Orf9b (Project 6). Although we will focus on SARS-CoV-2, related proteins from 19 other viruses will also be targeted. Using the QCRG Drug Discovery Platform, we will perform screens on these targets, involving fragment campaigns, virtual library docking, and high-throughput screens, to discover inhibitors. These inhibitors will be optimized using cycles of design, structure determination, and testing. In vitro and in vivo pharmacokinetics as well as activity in cellular and mouse models of infection will be carried out, followed by studies involving oral bioavailability, clearance, permeability, solubility, metabolic liabilities, toxicity and efficacy. The final goal of each Project is an Optimized Lead ready for clinical development at Roche. 

Throughout, we will exploit an integrated suite of experimental and computational technologies provided by eight Cores. The Biochemistry Core will provide purified material for the Screening Core, while the structures of  targets and compounds will be determined  through the Cryo-EM, Cryo-ET and crystallography capabilities of the Structural Biology Core. State-of-the-art mass spectrometry in the Proteomics Core will provide mechanistic insight into drug-protein relationships. The Medicinal Chemistry Core will optimize potent on-target compounds and work closely with the In Vitro Virology Core and In Vivo Virology Core to measure and optimize antiviral activity. The Integrative Modeling Core will provide computational support to structure determination and inhibitor discovery throughout the QCRG Drug Discovery Platform. The Administrative Core will help to foster a collaborative environment and will manage the Mentored Project Awards and the Developmental Research Project program, which will bring in new investigators.
 The QCRG AViDD Program will discover and develop inhibitors targeting key viral proteins. Innovation comes from using cutting-edge techniques individually and in combination with each other as well as from the viral proteins and processes targeted (e.g., viral enzymes that act to suppress host immune response). Impact comes from the development of clinical candidates with potent in vivo activity and from the development of a readily shared platform of technologies and target strategies for also treating future pandemics.

There will be an event on Monday, January 24th to discuss the ongoing progress related to the AViDD grant.

LEAD INVESTIGATORS:

Nevan Krogan, QBI UCSF (Lead PI of the Administrative Core and Proteomics Core) is the director of QBI and a leader in connecting systems approaches with mechanistic insight to unravel basic biology of pathogens, such as SARS-CoV-2, HIV, zika, Ebola and dengue. He has led numerous large, collaborative center grants from NIH on a variety of different diseases, from HIV to cancer, and spearheaded the QCRG in early 2020, recruiting scientists from all over the world to study and combat COVID19.

Robert Stroud, QBI UCSF (Lead PI of the Protein Biochemistry Core and Structural Biology Core) is a world-recognized crystallographer with major contributions to structure-based drug design, the study of membrane proteins and HIV integrase and viral proteases.

Michelle Arkin, QBI UCSF (Lead PI of the Screening Core) is widely known for innovations in high-throughput screening (HTS) and fragment discovery and for 14 years has co-run the UCSF Small Molecule Discovery Center with Adam Renslo.

Adam Renslo, QBI UCSF (Lead PI of the Medicinal Chemistry Core) has a Pharma med chem background and deep experience in hit-to-lead and lead optimization, with a longstanding interest in antimicrobial chemotherapy.

David Agard, QBI UCSF (Lead PI of the Structural Biology Core) is a leader in developing Cryo-EM techniques and their applications.

Andrej Sali, QBI UCSF (Lead PI of the Integrative Modeling Core) is a world expert on integrative modeling of protein machines and developed widely used software, such as IMP and MODELLER.

Melanie Ott, Gladstone Institutes/QBI UCSF (Lead PI of the In Vitro Virology Core and In Vivo Virology Core) is the director of the Gladstone Institute of Virology and recognized for her contributions to HIV Cure research and the pathogenesis of hepatitis C virus, zika virus and SARS-CoV-2 infections.

Adolfo Garcia-Sastre, Icahn School of Medicine at Mount Sinai, New York (Lead PI of the In Vivo Virology Core and In Vitro Virology Core) is the director of one of five NIAID-funded Centers of Excellence for Influenza Research and Surveillance and an expert on the molecular biology of negative-strand RNA viruses.

Danielle Swaney, QBI UCSF (Lead PI of the Proteomics Core) is a junior faculty at UCSF, an expert in mass spectrometry and Director of the Thermo Fisher Scientific Proteomics Facility for Disease Target Discovery located at UCSF/Gladstone.

Kevan Shokat, QBI UCSF (Lead PI of Project 1 and Project 4) is among the world’s foremost chemical biologists and has had an outsize impact on drug discovery for difficult targets.

Charles Craik, QBI UCSF (Lead PI of Project 2) is a world leader in protease structure-function, with a longstanding interest in antivirals.

William DeGrado, QBI UCSF (Lead PI of Project 3) is an expert in peptide chemistry, protein design, and drug discovery.

Danica Fujimori, QBI UCSF (Lead PI of Project 4) has deep experience in methyltransferases and demethylases.

James Fraser, QBI UCSF (Lead PI of Project 5 and Project 6) studies macromolecular structure and dynamics and created multi-temperature X-ray data collection approaches for ligand discovery campaigns.

CO-INVESTIGATORS:

Brian Shoichet, QBI UCSF (Co-I of Project 2, Project 4, Project 5, the Screening Core, and Medicinal Chemistry Core) is an expert in molecular docking, structure-based inhibitor discovery and artifact detection in early discovery.

Jennifer Doudna, UC Berkeley, Gladstone Institutes, QBI UCSF (Co-I of Project 1 and the In Vitro Virology Core) is a Nobel laureate renowned for the discovery of CRISPR and RNA-protein studies.

Eddy Arnold, Rutgers University (Co-I of Project 2) is an expert in antiviral drug discovery and his crystal structures of HIV-1 RT drove the development of two anti-HIV drugs, etravirine and rilpivirine.

Luis Martinez, University of Texas at San Antonio (Co-I of the In Vitro Virology Core) is recognized for generating recombinant arenaviruses, influenza and zika viruses with plasmid-based reverse genetic approaches. His lab has access to a maximum containment BSL-4 laboratory.

Mathias Götte, University of Alberta, Canada (Co-I of Project 2) is the world leader in characterizing the inhibition mechanisms of remdesivir and molnupiravir and focuses on studying and targeting RNA viral replication, with applications to Ebola, Nipah, Lassa, RSV, and influenza.

Masoud Vedadi, University of Toronto, Canada (Co-I of Project 4) focuses on developing new high throughput biophysical and biochemical characterization and screening methods to discover selective inhibitors of methyltransferases.

Marco Vignuzzi, Institut Pasteur, France (Co-I of the In Vitro Virology Core and In Vivo Virology Core) monitors and predicts the evolution of RNA viruses for developing vaccines and antivirals.

Carla Saleh, Institut Pasteur, France (Co-I of the In Vitro Virology Core and In Vivo Virology Core) aims to understand the molecular and cellular aspects of antiviral immunity in insects.

Yifan Cheng, QBI UCSF (Co-I of the Structural Biology Core) is an electron microscopist who redefined the resolution limits of single-particle Cryo-EM to rival the atomic resolution of X-ray crystallography.

Tanja Kortemme, QBI UCSF (Co-I of the Biochemistry Core and Integrative Modeling Core) combines computer science, physics, chemistry, mathematics, engineering and biology to engineer new bioactive molecules.

Kliment Verba, QBI UCSF (Co-I of Project 6 and the Structural Biology Core) is a QBI Fellow who leverages Cryo-EM and high-throughput X-ray crystallography for drug discovery.

Ana Sesma, Icahn School of Medicine at Mount Sinai, New York (Co-I of the In Vitro Virology Core) was recently ranked in the top 5 female NIH-funded investigators and studies innate immune evasion by coronaviruses, zika, HIV, influenza, chikungunya and dengue using human primary cell systems.

Jian Jin, Icahn School of Medicine at Mount Sinai, New York (Co-I of the Medicinal Chemistry Core) is an internationally recognized medicinal chemist and chemical biologist with over 20 years of experience in small-molecule drug discovery.

Judd Hultquist, Northwestern University (Co-I of Project 2) is an expert in developing high-throughput, quantitative methods to assess genetic perturbations in primary cell models of infection.

Kris White, Icahn School of Medicine at Mount Sinai, New York (Co-I of the In Vivo Virology Core) studies influenza replication for target discovery and works towards generation of a universal influenza vaccine.

Randy Albrecht, Icahn School of Medicine at Mount Sinai, New York (Co-I of the In Vivo Virology Core) studies the replication, pathogenesis, transmission, and adaptation of respiratory viruses to new hosts.

Alan Ashworth, QBI UCSF (Co-I of Project 5) is the President of the UCSF Helen Diller Family Comprehensive Cancer Center and an expert in ADP-ribosylation signaling, advancing the concept of synthetic lethality to the clinic with his work on PARP inhibitors.

Davide Ruggero, QBI UCSF (Co-I of Project 1) made numerous breakthrough discoveries in translational machinery and is, with Kevan Shokat, the scientific founder of eFFECTOR, a company testing the selective translation inhibitor zotatifin in patients with mild-to-moderate COVID19.

Gregory Towers, University College London (Co-I of the In Vitro Virology Core) studies virus-host interactions of HIV and SARS-CoV-2 and their relationship to the innate immune system to develop novel antivirals.

Michael Keiser, QBI UCSF (Co-I of the Integrative Modeling Core) develops new approaches to address core challenges in systems pharmacology, such as elucidation of multitarget small-molecule mechanisms and delineation of pharmacological circuits.

Jason Gestwicki, QBI UCSF (Co-I of the Screening Core) uses a chemical biology strategy that includes the discovery and optimization of new chemical inhibitors.

Pedro Beltrao, Instituto Gulbenkian de Ciencia (Co-I of the Integrative Modeling Core) is currently transitioning to ETH Zurich, studies the evolutionary dynamics and functional importance of post-translational regulatory networks and how they are rewired in the context of infection.

Clare Jolly, University College London (Co-I of the In Vitro Virology Core) uses expertise in molecular virology, cell biology and advanced imaging to understand the cell biology of viral infection.

Ignacia Echeverria Riesco, QBI UCSF (Co-I of the Integrative Modeling Core) has expertise in integrative structural modeling.

Robyn Kaake, QBI UCSF (Co-I of the Proteomics Core) has expertise in proteomics techniques with a focus on crosslinking (XL)-MS.

Lorena Zuliani-Alvarez, QBI UCSF (Co-I of the In Vitro Virology Core and Administrative Core) is a senior scientist and the Project Manager of QBI’s infectious disease portfolio, with expertise in molecular virology.

Ursula Schulze-Gahmen, QBI UCSF (Co-I of Project 2) is an accomplished biochemist and structural biologist with experience in viral protein structures and the regulation of HIV transcription.

Manon Eckhardt, QBI UCSF (Co-I of the Administrative Core) is a molecular systems virologist, and project manager with experience in science outreach and DEI programs.

PROJECTS


RNA virus families have great genetic heterogeneity that allows wide tropism and cross-species transmission. This group evolved to maximize the manipulation of the cellular machinery for viral replication and the antagonism or evasion of conserved cellular pathways aiming to restrict viral infection. For successful replication, all RNA viruses must complete five stages. First, key proteins in the viral envelope bind to target cell receptors and fuse with the host cell membrane (1-viral entry). Once in the cell cytosol, viral RNA is translated to make the viral proteins that are involved in the generation of the replication complex (2-RNA translation). Viral replication occurs inside cytoplasmic replication organelles or double membrane vesicles that protect the virus RNA from being detected (3-viral replication). Structural viral proteins are produced and package full-length genomes to complete virion formation (4-viral assembly). Viral particles undergo maturation through the ER-Golgi organelles, leading finally to viral egress from the cells (5-viral release). An exquisite balance between viruses and hosts must be achieved, where a virus must silence innate immune activation to complete its life cycle in the cell. A common strategy is to target essential steps of the viral lifecycle to inhibit viral replication, transmission and pathogenicity. The Projects developed by the QCRG AViDD Program aim to disrupt key processes at different stages that can be used alone or in combinations to suppress viral infection and disease.

Project 1: Targeting Viral RNA Using a Sequence Programmable Small Molecule-Oligonucleotide Conjugate (Lead: Shokat; Co-I: Doudna, Ruggero)

Project 2: Developing Antivirals Targeting Proteases and Polymerases of Coronaviruses, Picornaviruses and Bunyavirales (Lead: Craik; Co-I: Arnold, Götte, Schulze-Gahmen, Hultquist, Shoichet)

Project 3: Targeting Viroporins and Coronavirus M Protein (Lead: DeGrado; Co-I: Stroud, Hong)

Project 4: Development of Novel Antivirals Targeting Viral RNA Methylation (Lead: Fujimori; Co-I: Shokat, Vedadi, Shoichet)

Project 5: Inhibiting Viral Macrodomains Using Structure-Based Design (Lead: Fraser; Co-I: Shoichet, Ashworth)


CORES


We aim to advance targets and compounds for antiviral drug discovery. The team has expertise in drug discovery from target identification and characterization to Lead Optimization. Using the QCRG Drug Discovery Platform, each of the six Projects will be supported by eight Cores. Overall, we will follow the traditional, iteractive workflow of drug discovery, but each Project and Core includes innovative facets that reflect the unique specialties of the investigators.
The 5-year program will deliver 3–6 Optimized Lead molecules to
 Roche and potentially other partners for preclinical and clinical 
development. Graduation from each stage of the drug discovery
 process will follow design criteria that align with pharmaceutical
 company standards and will be informed by our Target Product
 Profile for an oral antiviral agent
.

Biochemistry Core (Lead: Stroud; Co-I: Kortemme, Fraser)

Screening Core (Lead: Arkin; Co-I:Shoichet, Fraser, Gestwicki)

Medicinal Chemistry Core (Lead: Renslo; Co-I: Shoichet, Jin)

Structural Biology Core (Lead: Agard; Co-I: Verba, Cheng, Stroud, Fraser)

Integrative Modeling Core (Lead: Sali; Co-I: Echeverria, Beltrao, Keiser, Kortemme)

In Vitro Virology Core (Lead: Ott; Co-I: Garcia-Sastre, Towers, Jolly, Vignuzzi, Sesma, Saleh, Martinez, Zuliani-Alvarez, Doudna)

In Vivo Virology Core (Lead: Garcia-Sastre; Co-I: White, Albrecht, Vignuzzi, Saleh, Ott)

Proteomics Core (Lead: Swaney; Co-I: Kaake, Krogan)

Administrative Core (Lead: Krogan; Co-I: Zuliani-Alvarez, Eckhardt)

Agarwal DK, Nandwana V, Henrich SE, Josyula VPVN, Thaxton CS, Qi C, Simons LM, Hultquist JF, Ozer EA, Shekhawat GS, Dravid VP. Highly sensitive and ultra-rapid antigen-based detection of SARS-CoV-2 using nanomechanical sensor platform. Biosens Bioelectron. 2022 Jan 1;195:113647. PMCID: PMC8445766

Asarnow D, Wang B, Lee W-H, Hu Y, Huang C-W, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Ary B, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Seah SGK, Chan CEZ, Connelly E, Young NJ, Maurer-Stroh S, Renia L, Hanson BJ, Rosa-Calatrava M, Manglik A, Cheng Y, Craik CS, Wang C-I. Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Cell. 2021 Jun 10;184(12):3192–3204.e16. PMCID: PMC8064868

Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, Batra J, Richards AL, Stevenson E, Gordon DE, Rojc A, Obernier K, Fabius JM, Soucheray M, Miorin L, Moreno E, Koh C, Tran QD, Hardy A, Robinot R, Vallet T, Nilsson-Payant BE, Hernandez- Armenta C, Dunham A, Weigang S, Knerr J, Modak M, Quintero D, Zhou Y, Dugourd A, Valdeolivas A, Patil T, Li Q, Hüttenhain R, Cakir M, Muralidharan M, Kim M, Jang G, Tutuncuoglu B, Hiatt J, Guo JZ, Xu J, Bouhaddou S, Mathy CJP, Gaulton A, Manners EJ, Félix E, Shi Y, Goff M, Lim JK, McBride T, O’Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, De Wit E, Leach AR, Kortemme T, Shoichet B, Ott M, Saez- Rodriguez J, tenOever BR, Mullins RD, Fischer ER, Kochs G, Grosse R, García-Sastre A, Vignuzzi M, Johnson JR, Shokat KM, Swaney DL, Beltrao P, Krogan NJ. The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685–712.e19. PMCID: PMC7321036 Bracken CJ, Lim SA, Solomon P, Rettko NJ, Nguyen DP, Zha BS, Schaefer K, Byrnes JR, Zhou J, Lui I, Liu J, Pance K, QCRG Structural Biology Consortium, Zhou XX, Leung KK, Wells JA. Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2. Nat Chem Biol. 2021 Jan;17(1):113–121. PMCID: PMC8356808

Cakir M, Obernier K, Forget A, Krogan NJ. Target Discovery for Host-Directed Antiviral Therapies: Application of Proteomics Approaches. mSystems. 2021 Sep 14;e0038821. PMID: 34519533

Edward PR, Reyna ME, Daly MK, Hultquist JF, Muller WJ, Ozer EA, Lorenzo-Redondo R, Seed PC, Simons LM, Sheehan K, Staples J, Kociolek L. Screening Students and Staff for Asymptomatic Coronavirus Disease 2019 in Chicago Schools. J Pediatr. 2021 Dec;239:74–80.e1. PMCID: PMC8372436

Escalera A, Gonzalez-Reiche AS, Aslam S, Mena I, Pearl RL, Laporte M, Fossati A, Rathnasinghe R, Alshammary H, van de Guchte A, Bouhaddou M, Kehrer T, Zuliani-Alvarez L, Meekins DA, Balaraman V, McDowell C, Richt JA, Bajic G, Sordillo EM, Krogan N, Simon V, Albrecht RA, van Bakel H, Garcia-Sastre A, Aydillo T. SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage [Preprint]. 2021. Available from: http://dx.doi.org/10.1101/2021.08.05.455290 Fabius JM, Krogan NJ. Creating collaboration by breaking down scientific barriers. Cell. 2021 Apr 29;184(9):2271–2275. PMID: 33765441

Gordon CJ, Lee HW, Tchesnokov EP, Perry JK, Feng JY, Bilello JP, Porter DP, Götte M. Efficient incorporation and template-dependent polymerase inhibition are major determinants for the broad-spectrum antiviral activity of remdesivir. J Biol Chem. 2021 Dec 22;101529. PMCID: PMC8695323 Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang X-P, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O’Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang H-Y, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d’Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 Jul;583(7816):459–468. PMCID: PMC7431030

Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O’Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Hüttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbølle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li Y-L, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR 3rd, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH Jr, Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D, QCRG Structural Biology Consortium, Hodder AJ, Shun-Shion AS, Williams DM, White KM, Rosales R, Kehrer T, Miorin L, Moreno E, Patel AH, Rihn S, Khalid MM, Vallejo-Gracia A, Fozouni P, Simoneau CR, Roth TL, Wu D, Karim MA, Ghoussaini M, Dunham I, Berardi F, Weigang S, Chazal M, Park J, Logue J, McGrath M, Weston S, Haupt R, Hastie CJ, Elliott M, Brown F, Burness KA, Reid E, Dorward M, Johnson C, Wilkinson SG, Geyer A, Giesel DM, Baillie C, Raggett S, Leech H, Toth R, Goodman N, Keough KC, Lind AL, Zoonomia Consortium, Klesh RJ, Hemphill KR, Carlson-Stevermer J, Oki J, Holden K, Maures T, Pollard KS, Sali A, Agard DA, Cheng Y, Fraser JS, Frost A, Jura N, Kortemme T, Manglik A, Southworth DR, Stroud RM, Alessi DR, Davies P, Frieman MB, Ideker T, Abate C, Jouvenet N, Kochs G, Shoichet B, Ott M, Palmarini M, Shokat KM, García-Sastre A, Rassen JA, Grosse R, Rosenberg OS, Verba KA, Basler CF, Vignuzzi M, Peden AA, Beltrao P, Krogan NJ. Comparative host-coronavirus protein interaction networks reveal panviral disease mechanisms. Science. 2020 Dec 4;370(6521). Available from: http://dx.doi.org/10.1126/science.abe9403 PMCID: PMC7808408

Gupta M, Azumaya CM, Moritz M, Pourmal S, Diallo A, Merz GE, Jang G, Bouhaddou M, Fossati A, Brilot AF, Diwanji D, Hernandez E, Herrera N, Kratochvil HT, Lam VL, Li F, Li Y, Nguyen HC, Nowotny C, Owens TW, Peters JK, Rizo AN, Schulze-Gahmen U, Smith AM, Young ID, Yu Z, Asarnow D, Billesbølle C, Campbell MG, Chen J, Chen K-H, Chio US, Dickinson MS, Doan L, Jin M, Kim K, Li J, Li Y-L, Linossi E, Liu Y, Lo M, Lopez J, Lopez KE, Mancino A, Moss FR, Paul MD, Pawar KI, Pelin A, Pospiech TH, Puchades C, Remesh SG, Safari M, Schaefer K, Sun M, Tabios MC, Thwin AC, Titus EW, Trenker R, Tse E, Tsui TKM, Wang F, Zhang K, Zhang Y, Zhao J, Zhou F, Zhou Y, Zuliani-Alvarez L, QCRG Structural Biology Consortium, Agard DA, Cheng Y, Fraser JS, Jura N, Kortemme T, Manglik A, Southworth DR, Stroud RM, Swaney DL, Krogan NJ, Frost A, Rosenberg OS, Verba KA. CryoEM and AI reveal a structure of SARSCoV- 2 Nsp2, a multifunctional protein involved in key host processes. bioRxiv [Preprint]. 2021 May 11; Available from: http://dx.doi.org/10.1101/2021.05.10.443524 PMCID: PMC8132225

Haas P, Muralidharan M, Krogan NJ, Kaake RM, Hüttenhain R. Proteomic Approaches to Study SARSCoV- 2 Biology and COVID-19 Pathology. J Proteome Res. 2021 Feb 5;20(2):1133–1152. PMCID: PMC7839417

Kociolek LK, Patel AB, Hultquist JF, Ozer EA, Simons LM, McHugh M, Muller WJ, Lorenzo-Redondo R. Viral whole-genome sequencing to assess impact of universal masking on SARS-CoV-2 transmission among pediatric healthcare workers. Infect Control Hosp Epidemiol. 2021 Oct 1;1–5. PMID: 34593066

Lindan CP, Desai M, Boothroyd D, Judson T, Bollyky J, Sample H, Weng Y, Cheng Y, Dahlen A, Hedlin H, Grumbach K, Henne J, Garcia S, Gonzales R, Craik CS, Maldonado Y, Rutherford G. Design of a population-based longitudinal cohort study of SARS-CoV-2 incidence and prevalence among adults in the San Francisco Bay Area. Ann Epidemiol. 2021 Nov 17; Available from: http://dx.doi.org/10.1016/j.annepidem.2021.11.001 PMCID: PMC8596645

Mahoney M, Damalanka VC, Tartell MA, Chung DH, Lourenço AL, Pwee D, Mayer Bridwell AE, Hoffmann M, Voss J, Karmakar P, Azouz NP, Klingler AM, Rothlauf PW, Thompson CE, Lee M, Klampfer L, Stallings CL, Rothenberg ME, Pöhlmann S, Whelan SPJ, O’Donoghue AJ, Craik CS, Janetka JW. A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. Proc Natl Acad Sci U S A. 2021 Oct 26;118(43). Available from: http://dx.doi.org/10.1073/pnas.2108728118 PMID: 34635581

Miorin L, Kehrer T, Sanchez-Aparicio MT, Zhang K, Cohen P, Patel RS, Cupic A, Makio T, Mei M, Moreno E, Danziger O, White KM, Rathnasinghe R, Uccellini M, Gao S, Aydillo T, Mena I, Yin X, Martin-Sancho L, Krogan NJ, Chanda SK, Schotsaert M, Wozniak RW, Ren Y, Rosenberg BR, Fontoura BMA, García-Sastre A. SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28344–28354. PMCID: PMC7668094

O’Donnell HR, Tummino TA, Bardine C, Craik CS, Shoichet BK. Colloidal Aggregators in Biochemical SARS-CoV-2 Repurposing Screens. J Med Chem. 2021 Dec 9;64(23):17530–17539. PMCID: PMC8665103

Reuschl A-K, Thorne LG, Zuliani-Alvarez L, Bouhaddou M, Obernier K, Hiatt J, Soucheray M, Turner J, Fabius JM, Nguyen GT, Swaney DL, Rosales R, White KM, Avilés P, Kirby IT, Melnyk JE, Shi Y, Zhang Z, Shokat KM, García-Sastre A, Jolly C, Towers GJ, Krogan NJ. Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant. bioRxiv [Preprint]. 2021 Feb 4; Available from: http://dx.doi.org/10.1101/2021.01.24.427991 PMCID: PMC7836107

Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE, Thompson MC, Diwanji D, Schaefer K, Anand AA, Dobzinski N, Zha BS, Simoneau CR, Leon K, White KM, Chio US, Gupta M, Jin M, Li F, Liu Y, Zhang K, Bulkley D, Sun M, Smith AM, Rizo AN, Moss F, Brilot AF, Pourmal S, Trenker R, Pospiech T, Gupta S, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, García-Sastre A, Ott M, Vignuzzi M, QCRG Structural Biology Consortium, Walter P, Manglik A. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science. 2020 Dec 18;370(6523):1473–1479. PMCID: PMC7857409

Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Carvalho Martins L, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, QCRG Structural Biology Consortium, Aimon A, Bennett JM, Brandao Neto J, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs MR, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, O’Brien P, Jura N, Ashworth A, Irwin JJ, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I. Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking. Sci Adv. 2021 Apr;7(16). Available from: http://dx.doi.org/10.1126/sciadv.abf8711 PMCID: PMC8046379

Souilmi Y, Lauterbur ME, Tobler R, Huber CD, Johar AS, Moradi SV, Johnston WA, Krogan NJ, Alexandrov K, Enard D. An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia. Curr Biol. 2021 Aug 23;31(16):3704. PMCID: PMC8381604

Syed AM, Ciling A, Khalid MM, Sreekumar B, Chen P-Y, Kumar GR, Silva I, Milbes B, Kojima N, Hess V, Shacreaw M, Lopez L, Brobeck M, Turner F, Spraggon L, Taha TY, Tabata T, Chen IP, Ott M, Doudna JA. Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles. medRxiv [Internet]. 2022 Jan 2; Available from: http://dx.doi.org/10.1101/2021.12.20.21268048 PMCID: PMC8722610

Syed AM, Taha TY, Tabata T, Chen IP, Ciling A, Khalid MM, Sreekumar B, Chen P-Y, Hayashi JM, Soczek KM, Ott M, Doudna JA. Rapid assessment of SARS-CoV-2-evolved variants using virus-like particles. Science. 2021 Dec 24;374(6575):1626–1632. PMID: 34735219

Thorne LG, Bouhaddou M, Reuschl A-K, Zuliani-Alvarez L, Polacco B, Pelin A, Batra J, Whelan MVX, Hosmillo M, Fossati A, Ragazzini R, Jungreis I, Ummadi M, Rojc A, Turner J, Bischof ML, Obernier K, Braberg H, Soucheray M, Richards A, Chen K-H, Harjai B, Memon D, Hiatt J, Rosales R, McGovern BL, Jahun A, Fabius JM, White K, Goodfellow IG, Takeuchi Y, Bonfanti P, Shokat K, Jura N, Verba K, Noursadeghi M, Beltrao P, Kellis M, Swaney DL, García-Sastre A, Jolly C, Towers GJ, Krogan NJ. Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature. 2021 Dec 23; Available from: http://dx.doi.org/10.1038/s41586-021-04352-y PMID: 34942634

Tummino TA, Rezelj VV, Fischer B, Fischer A, O’Meara MJ, Monel B, Vallet T, White KM, Zhang Z, Alon A,Schadt H, O’Donnell HR, Lyu J, Rosales R, McGovern BL, Rathnasinghe R, Jangra S, Schotsaert M, Galarneau J-R, Krogan NJ, Urban L, Shokat KM, Kruse AC, García-Sastre A, Schwartz O, Moretti F, Vignuzzi M, Pognan F, Shoichet BK. Drug-induced phospholipidosis confounds drug repurposing for SARSCoV-2. Science. 2021 Jul 30;373(6554):541–547. PMID: 34326236

Tutuncuoglu B, Cakir M, Batra J, Bouhaddou M, Eckhardt M, Gordon DE, Krogan NJ. The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2. Cancer Discov. 2020 Jul;10(7):916–921. PMCID: PMC7357668

Varona JF, Landete P, Lopez-Martin JA, Estrada V, Paredes R, Guisado-Vasco P, de Orueta LF, Torralba M, Fortún J, Vates R, Barberán J, Clotet B, Ancochea J, Carnevali D, Cabello N, Porras L, Gijón P, Monereo A, Abad D, Zúñiga S, Sola I, Rodon J, Izquierdo-Useros N, Fudio S, Pontes MJ, de Rivas B, de Velasco PG, Sopesén B, Nieto A, Gómez J, Avilés P, Lubomirov R, White KM, Rosales R, Yildiz S, Reuschl A-K, Thorne LG, Jolly C, Towers GJ, Zuliani-Alvarez L, Bouhaddou M, Obernier K, Enjuanes L, Fernández-Sousa JM, Krogan NJ, Jimeno JM, García-Sastre A, Plitidepsin – COVID-19 Study Group. Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization. [Preprint]. 2021. Available from: http://dx.doi.org/10.1101/2021.05.25.21257505

Wang R, Simoneau CR, Kulsuptrakul J, Bouhaddou M, Travisano KA, Hayashi JM, Carlson-Stevermer J, Zengel JR, Richards CM, Fozouni P, Oki J, Rodriguez L, Joehnk B, Walcott K, Holden K, Sil A, Carette JE, Krogan NJ, Ott M, Puschnik AS. Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses. Cell. 2021 Jan 7;184(1):106–119.e14. PMCID: PMC7723770

Weinberg ZY, Hilburger CE, Kim M, Cao L, Khalid M, Elmes S, Diwanji D, Hernandez E, Lopez J, Schaefer K, Smith AM, Zhou F, QCRG Structural Biology Consortium, Renuka Kumar G, Ott M, Baker D, El-Samad H. Sentinel cells enable genetic detection of SARS-CoV-2 Spike protein. bioRxiv [Preprint]. 2021 Apr 20; Available from: http://dx.doi.org/10.1101/2021.04.20.440678 PMCID: PMC8077567

White KM, Rosales R, Yildiz S, Kehrer T, Miorin L, Moreno E, Jangra S, Uccellini MB, Rathnasinghe R, Coughlan L, Martinez-Romero C, Batra J, Rojc A, Bouhaddou M, Fabius JM, Obernier K, Dejosez M, Guillén MJ, Losada A, Avilés P, Schotsaert M, Zwaka T, Vignuzzi M, Shokat KM, Krogan NJ, García-Sastre A. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science. 2021 Feb 26;371(6532):926–931. PMCID: PMC7963220

Whitman JD, Hiatt J, Mowery CT, Shy BR, Yu R, Yamamoto TN, Rathore U, Goldgof GM, Whitty C, Woo JM, Gallman AE, Miller TE, Levine AG, Nguyen DN, Bapat SP, Balcerek J, Bylsma SA, Lyons AM, Li S, Wong AW-Y, Gillis-Buck EM, Steinhart ZB, Lee Y, Apathy R, Lipke MJ, Smith JA, Zheng T, Boothby IC, Isaza E, Chan J, Acenas DD 2nd, Lee J, Macrae TA, Kyaw TS, Wu D, Ng DL, Gu W, York VA, Eskandarian HA, Callaway PC, Warrier L, Moreno ME, Levan J, Torres L, Farrington LA, Loudermilk RP, Koshal K, Zorn KC, Garcia-Beltran WF, Yang D, Astudillo MG, Bernstein BE, Gelfand JA, Ryan ET, Charles RC, Iafrate AJ, Lennerz JK, Miller S, Chiu CY, Stramer SL, Wilson MR, Manglik A, Ye CJ, Krogan NJ, Anderson MS, Cyster JG, Ernst JD, Wu AHB, Lynch KL, Bern C, Hsu PD, Marson A. Evaluation of SARS-CoV-2 serology assays reveals a range of test performance. Nat Biotechnol. 2020 Oct;38(10):1174–1183. PMCID: PMC7740072

Yoshida M, Worlock KB, Huang N, Lindeboom RGH, Butler CR, Kumasaka N, Conde CD, Mamanova L, Bolt L, Richardson L, Polanski K, Madissoon E, Barnes JL, Allen-Hyttinen J, Kilich E, Jones BC, de Wilton A, Wilbrey-Clark A, Sungnak W, Pett JP, Weller J, Prigmore E, Yung H, Mehta P, Saleh A, Saigal A, Chu V, Cohen JM, Cane C, Iordanidou A, Shibuya S, Reuschl A-K, Herczeg IT, Argento AC, Wunderink RG, Smith SB, Poor TA, Gao CA, Dematte JE, Reynolds G, Haniffa M, Bowyer GS, Coates M, Clatworthy MR, Calero-Nieto FJ, Göttgens B, O’Callaghan C, Sebire NJ, Jolly C, de Coppi P, Smith CM, Misharin AV, Janes SM, Teichmann SA, Nikolić MZ, Meyer KB. Local and systemic responses to SARS-CoV-2 infection in children and adults. Nature. Nature Publishing Group; 2021 Dec 22;1–10.

ARTICLES IN PRESS

W. R. Arnold, D. Asarnow and Y. Cheng. Classifying liganded states in heterogeneous single-particle cryo-EM datasets. 2022. Microscopy (Oxford, England); DOI: 10.1093/jmicro/dfab044

A. Escalera, A. S. Gonzalez-Reiche, S. Aslam, I. Mena, R. L. Pearl, M. Laporte, A. Fossati, R. Rathnasinghe, H. Alshammary, A. van de Guchte, M. Bouhaddou, T. Kehrer, L. Zuliani-Alvarez, D. A. Meekins, V. Balaraman, C. McDowell, J. A. Richt, G. Bajic, E. M. Sordillo, N. Krogan, V. Simon, R. A. Albrecht, H. van Bakel, A. Garcia-Sastre, T. Aydillo. SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage. 2022. Cell Host and Microbe (Accepted)

R. Howell, M. Clarke, A-K. Reuschl, T. Chen, S. Abott-Imboden, M. Singer, D. Lowe, C. Bennett, B. Chain, C. Jolly and J. Fisher. Executable network of SARS-CoV-2-Host interaction predicts drug combination treatments. 2022. Npj Digital Medicine (Accepted)

E.A. Ozer, L.M. Simons, O.M. Adewumi, A.A. Fowotade, E.C. Omoruyi, J.A. Adeniji, T.J. Dean, J. Zayas, P.P. Bhimalli, M.K. Ash, A. Godzik, J.R. Schneider, J.I. Mamede, B.O. Taiwo, J.F. Hultquist and R. Lorenzo-Redondo. Multiple expansions of globally uncommon SARS-CoV-2 lineages in Nigeria. Nature Communications (In Press)

S. Siddiqui, K. Bowman, A. Zhu, S. Fischinger, S. Beger, J. Maron, Y. Bartsch, C. Atyeo, M. Gorman, A. Yanis, J. Hultquist, R. Lorenzo-Redondo, E. Ozer, L. Simons, R. Talj, D. Rankin, L. Chapman, K. Meade, J. Steinhart, S. Mullane, S. Siebert, H. Streeck, P. Sabeti, N. Halasa, E. Musk, D. Barouch, A. Menon, E. Nilles, D. Lauffenburger, and G. Alter. Serological markers of SARS-CoV-2 reinfection. 2022. mBio. (In Press)

J. Varona, P. Landete, J. A. Lopez-Martin, V. Estrada, R. Paredes, P. Guisado-Vasco, L. Fernandez de Orueta, M. Torralba, J. Fortun, R. Vates, J. Barberan, B. Clotet, J. Ancochea, D. Carnevali, N. Cabello, L. Porras, P. Gijon, A. Monereo, D. Abad, S. Zuñiga, I. Sola, J. Rodon, J. Vergara-Alert, N. Izquierdo-Useros, S. Fudio, M. J. Pontes, B. de Rivas, P. Giron de Velasco, A. Nieto, J. Gomez, P. Aviles, R. Lubomirov, A. Belgrano, B. Sopesen, K. White, R. Rosales, S. Yildiz, A.-K. Reuschl, L. Thorne, C. Jolly, G. Towers, L. Zuliani-Alvarez, M. Bouhaddou, K. Obernier, B. McGovern, M. L. Rodriguez, L. Enjuanes, J. M. Fernandez-Sousa, N. J. Krogan, J. M. Jimeno, and A. Garcia-Sastre. Pre-clinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19. 2022. Life Science Alliance. DOI: 10.26508/lsa.202101200