ArticleNature communications2021
Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
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174citing papers in PubMed
16.7field-weighted citation impact, top 1% of its field
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Who cites it
174 citing papers in PubMed, 288 citations in OpenAlex.
- Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171.Antimicrobial agents and chemotherapy · 2024Trial
- Safety, Tolerability, and Pharmacokinetics of Intravenous Doses of PF-07304814, a Phosphate Prodrug Protease Inhibitor for the Treatment of SARS-CoV-2, in Healthy Adult Participants.Clinical pharmacology in drug development · 2022Trial
- Orally Bioavailable SARS-CoV-2 Protease Inhibitors Bearing a Hydroxymethyl Ketone Warhead.Viruses · 2026Article
- Inhibitory effects and structural analysis of drug candidate PF-07817883 against coronaviral main proteases (MJournal of structural biology: X · 2026Article
- Peptidomimetic α,β-Unsaturated Ethyl Esters Are Irreversible Inactivators of Human Cathepsin L and Are Potent Inhibitors of SARS-CoV-2 in Cellular Models of COVID-19.Journal of medicinal chemistry · 2026Article
- Next-generation inhibitors of SARS-CoV-2 MNature communications · 2026Article
- Unbiased cleavage site prediction uncovers viral antagonism of host innate immunity by SARS-CoV-2 3C-like protease.JCI insight · 2026Article
- Identification of a Quinolone-Based Scaffold as a Dual SARS-COV-2 PLᵖʳᵒ and Mᵖʳᵒ Inhibitor: An Integrated Molecular Modeling and In-vitro Evaluation Approach.Drug design, development and therapy · 2026Article
- Identification of broad-spectrum MJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Review
- A luminescent attenuated SARS-CoV-2 for the identification and validation of drug-resistant mutants.Journal of virology · 2025Article
- Inhibitor-induced dimerization mediates lufotrelvir resistance in mutants of SARS-CoV-2 3C-like protease.Protein science : a publication of the Protein Society · 2025Article
- Review
- The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D.Virologica Sinica · 2025Article
- Article
- Identification of potential SARS-CoV-2 inhibitors among well-tolerated drugs using drug repurposing and in vitro approaches.Scientific reports · 2025Article
- Utility of Biomarker-Informed Drug Interaction Evaluation in Drug Development and Regulatory Decision Making.Clinical pharmacology and therapeutics · 2025Review
- Key advances in the development of reversible covalent inhibitors.Future medicinal chemistry · 2025Article
- Research Progress on the Structure and Function, Immune Escape Mechanism, Antiviral Drug Development Methods, and Clinical Use of SARS-CoV-2 MMolecules (Basel, Switzerland) · 2025Review
114 more citing papers are in PubMed but not listed here.
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Authors and funding
52 authors at 7 institutions in 2 countries.
Britton Boras *Worldwide Research and Development, Pfizer Inc, La Jolla, CA, 92121, USA.
Rhys M Jones *Worldwide Research and Development, Pfizer Inc, La Jolla, CA, 92121, USA. rhys.jones@pfizer.com.ORCID 0000-0002-5263-9194
Brandon J AnsonDepartment of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.ORCID 0000-0003-2670-974X
Dan ArensonWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Lisa AschenbrennerWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Malina A BakowskiCalibr, a division of The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID 0000-0002-3337-6528
Nathan BeutlerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID 0000-0003-3240-9524
Joseph BinderWorldwide Research and Development, Pfizer Inc, La Jolla, CA, 92121, USA.
Emily ChenCalibr, a division of The Scripps Research Institute, La Jolla, CA, 92037, USA.
Heather EngWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.ORCID 0000-0002-2914-3967
Holly HammondDepartment of Microbiology and Immunology University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Jennifer HammondWorldwide Research and Development, Pfizer Inc., Collegeville, PA, 19426, USA.
Robert E HauptDepartment of Microbiology and Immunology University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Robert HoffmanWorldwide Research and Development, Pfizer Inc, La Jolla, CA, 92121, USA.ORCID 0000-0002-2030-9094
Eugene P KadarWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Rob KaniaWorldwide Research and Development, Pfizer Inc, La Jolla, CA, 92121, USA.
Emi KimotoWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.ORCID 0000-0003-1284-2769
Melanie G KirkpatrickCalibr, a division of The Scripps Research Institute, La Jolla, CA, 92037, USA.
Lorraine LanyonWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Emma K LendyDepartment of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA.
Jonathan R LillisWorldwide Research and Development, Pfizer Inc, Sandwich, CT13 9ND, UK.
James LogueDepartment of Microbiology and Immunology University of Maryland School of Medicine, Baltimore, MD, 21201, USA.ORCID 0000-0002-7410-9741
Suman A LuthraWorldwide Research and Development, Pfizer Inc, Cambridge, MA, 02139, USA.
Chunlong MaDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA.ORCID 0000-0002-5766-8189
Stephen W MasonWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Marisa E McGrathDepartment of Microbiology and Immunology University of Maryland School of Medicine, Baltimore, MD, 21201, USA.ORCID 0000-0002-7451-4958
Stephen NoellWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
R Scott ObachWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Matthew N O' BrienWorldwide Research and Development, Pfizer Inc, Lake Forest, IL, 60045, USA.
Rebecca O'ConnorWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Kevin OgilvieWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.ORCID 0000-0002-1024-2172
Dafydd OwenWorldwide Research and Development, Pfizer Inc, Cambridge, MA, 02139, USA.
Martin PetterssonWorldwide Research and Development, Pfizer Inc, Cambridge, MA, 02139, USA.
Matthew R ReeseWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.ORCID 0000-0002-1066-2652
Thomas F RogersDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID 0000-0001-9756-327X
Romel RosalesDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-5326-4753
Michelle I RossulekWorldwide Research and Development, Pfizer Inc, Cambridge, MA, 02139, USA.
Jean G SathishWorldwide Research and Development, Pfizer Inc., Pearl River, NY, 10965, USA.
Norimitsu ShiraiWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Claire SteppanWorldwide Research and Development, Pfizer Inc, Groton, CT, 06340, USA.
Martyn TicehurstWorldwide Research and Development, Pfizer Inc, Sandwich, CT13 9ND, UK.
Lawrence W UpdykeWorldwide Research and Development, Pfizer Inc, Cambridge, MA, 02139, USA.
Stuart WestonDepartment of Microbiology and Immunology University of Maryland School of Medicine, Baltimore, MD, 21201, USA.ORCID 0000-0001-9840-2953
Yuao ZhuWorldwide Research and Development, Pfizer Inc., Pearl River, NY, 10965, USA.
Kris M WhiteDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-0889-0506
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-6551-1827
Jun WangDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA.ORCID 0000-0002-4845-4621
Arnab K ChatterjeeCalibr, a division of The Scripps Research Institute, La Jolla, CA, 92037, USA.
Andrew D MesecarDepartment of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
Matthew B FriemanDepartment of Microbiology and Immunology University of Maryland School of Medicine, Baltimore, MD, 21201, USA.ORCID 0000-0003-0107-0775
Annaliesa S AndersonWorldwide Research and Development, Pfizer Inc., Pearl River, NY, 10965, USA.ORCID 0000-0002-6413-1718
Charlotte AllertonWorldwide Research and Development, Pfizer Inc, Cambridge, MA, 02139, USA.ORCID 0000-0001-8665-159X
Pfizer (United States) · USScripps Research Institute · USUniversity of Maryland, Baltimore · USIcahn School of Medicine at Mount Sinai · USPurdue University West Lafayette · USPfizer (United Kingdom) · GBUniversity of Arizona · US
Funding
COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTER: UNIVERSAL INFLUENZA VACCINE RESEARCH75N93019C00051 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KRAMMER, FLORIAN · 2019 to 2025
$105.4MSARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2MTechnology Development Project - Increasing the complexity of ex vivo human airway models for studying immune response to viral infectionU19AI142733 · NIAID · JACKSON LABORATORY · PI Adolfo Garcia-Sastre, Anna Karolina Palucka · 2019 to 2026
$23.1MRole of Diabetes in MERS Coronavirus PathogenesisR01AI148166 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI FRIEMAN, MATTHEW BRYAN · 2020 to 2023
$2.3MHigh Throughput Screening of Inhibitors Targeting the Enterovirus A71 and D68 2A ProteasesR01AI147325 · NIAID · UNIVERSITY OF ARIZONA · PI WANG, JUN · 2019 to 2022
$1.7MBroad Spectrum Anti-viral Compounds Targeting the SKI ComplexR21AI153480 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI FRIEMAN, MATTHEW BRYAN · 2020 to 2021
$425kSARS-CoV-2 and AutophagyR21AI158134 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI JACKSON, WILLIAM T · 2020 to 2020
$425kNIAID NIH HHS 75N93019C00051NIAID NIH HHS HHSN272201400007CNIAID NIH HHS HHSN272201400008CNIAID NIH HHS HHSN272201700060CNIAID NIH HHS R01 AI147325NIAID NIH HHS R01 AI148166NIAID NIH HHS R21 AI153480NIAID NIH HHS R21 AI158134NIAID NIH HHS U19 AI135972NIAID NIH HHS U19 AI142733
Abstract
COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.
Indexed as
COVID-19 Drug TreatmentAdenosine MonophosphateAlanineAnimalsChlorocebus aethiopsCoronavirus 229E, HumanCoronavirus 3C ProteasesCoronavirus Protease InhibitorsCOVID-19Disease Models, AnimalDrug DesignDrug SynergismDrug Therapy, CombinationHeLa CellsHumansIndoles3C-like proteinase, SARS-CoV-2Adenosine MonophosphateAlanineCoronavirus 3C ProteasesCoronavirus Protease InhibitorsIndolesLeucinelufotrelvirPyrrolidinonesremdesivir
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