A Quick Route to Multiple Highly Potent SARS‐CoV‐2 Main Protease Inhibitors

The COVID‐19 pathogen, SARS‐CoV‐2, requires its main protease (SC2MPro) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus f...

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Published inChemMedChem Vol. 16; no. 6; pp. 942 - 948
Main Authors Yang, Kai S., Ma, Xinyu R., Ma, Yuying, Alugubelli, Yugendar R., Scott, Danielle A., Vatansever, Erol C., Drelich, Aleksandra K., Sankaran, Banumathi, Geng, Zhi Z., Blankenship, Lauren R., Ward, Hannah E., Sheng, Yan J., Hsu, Jason C., Kratch, Kaci C., Zhao, Baoyu, Hayatshahi, Hamed S., Liu, Jin, Li, Pingwei, Fierke, Carol A., Tseng, Chien‐Te K., Xu, Shiqing, Liu, Wenshe Ray
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 18.03.2021
Wiley Subscription Services, Inc
ChemPubSoc Europe
Subjects
3C-like protease
60 APPLIED LIFE SCIENCES
A549 Cells
ACE2
Alanine - analogs & derivatives
Alanine - metabolism
Alanine - pharmacology
Angiotensin-converting enzyme 2
Animals
Antiviral Agents - chemical synthesis
Antiviral Agents - metabolism
Antiviral Agents - pharmacology
Antiviral drugs
antivirals
Catalytic Domain
Chemical bonds
Chemistry, Medicinal
Chlorocebus aethiops
Coronavirus 3C Proteases - antagonists & inhibitors
Coronavirus 3C Proteases - chemistry
Coronavirus 3C Proteases - metabolism
Covalent bonds
COVID-19
Crystallography
Cysteine - chemistry
Cysteine Proteinase Inhibitors - chemical synthesis
Cysteine Proteinase Inhibitors - metabolism
Cysteine Proteinase Inhibitors - pharmacology
Humans
Life Sciences & Biomedicine
main protease
Microbial Sensitivity Tests
Pathogenesis
Pharmacology & Pharmacy
Polypeptides
Protease
Protease inhibitors
Protein Binding
Proteinase inhibitors
Proteolysis
Pyrrolidinones - chemical synthesis
Pyrrolidinones - metabolism
Pyrrolidinones - pharmacology
reversible covalent inhibitors
SARS-CoV-2
SARS-CoV-2 - drug effects
SARS-CoV-2 - enzymology
Science & Technology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Vero Cells
Viral diseases
Viruses
COVID-19
3C-like protease
antivirals
reversible covalent inhibitors
SARS-CoV-2
EFFICACY
main protease
IDENTIFICATION
CORONAVIRUS
Online AccessGet full text
ISSN1860-7179
1860-7187
1860-7187
DOI10.1002/cmdc.202000924

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Abstract The COVID‐19 pathogen, SARS‐CoV‐2, requires its main protease (SC2MPro) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID‐19 treatment option. Guided by previous medicinal chemistry studies about SARS‐CoV‐1 main protease (SC1MPro), we have designed and synthesized a series of SC2MPro inhibitors that contain β‐(S‐2‐oxopyrrolidin‐3‐yl)‐alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active‐site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound, MPI3, has as a Ki value of 8.3 nM. Crystallographic analyses of SC2MPro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS‐CoV‐2‐induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS‐CoV‐2‐induced cytopathogenic effect in Vero E6 cells at 2.5–5 μM and A549/ACE2 cells at 0.16–0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID‐19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with ultra‐high antiviral potency. Small but strong: A series of SARS‐CoV‐2 MPro covalent inhibitors exhibit excellent activity. Protein crystallography analysis and a live virus‐based microneutralization assay found two of the most potent anti‐SARS‐CoV‐2 small molecules so far. Due to the urgent matter of the COVID‐19 pandemic, these two inhibitors could be quickly advanced to preclinical and clinical tests for COVID‐19.
AbstractList The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M(Pro)) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1M(Pro)), we have designed and synthesized a series of SC2M(Pro) inhibitors that contain beta-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2M(Pro) active-site cysteine C145. All inhibitors display high potency with K-i values at or below 100 nM. The most potent compound, MPI3, has as a K-i value of 8.3 nM. Crystallographic analyses of SC2M(Pro) bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5 mu M and A549/ACE2 cells at 0.16-0.31 mu M. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2M(Pro) inhibitors with ultra-high antiviral potency.
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M Pro ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replication in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1M Pro ), we have designed and synthesized a series of SC2M Pro inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2M Pro active site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound MPI3 has as a Ki value as 8.3 nM. Crystallographic analyses of SC2M Pro bound to 7 inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors MPI5 and MPI8 completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5–5 μM and A549/ACE2 cells at 0.16–0.31 μM. Their virus inhibition potency is much higher than some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2M Pro inhibitors with ultra-high antiviral potency. We designed and synthesized a series of SARS-CoV-2 M Pro covalent inhibitors that exhibited excellent inhibitory activity. Protein crystallography analysis and a live virus-based microneutralization assay found two most potent anti-SARS-CoV-2 small molecules so far. Due to the urgent matter of the COVID-19 pandemic, these two inhibitors may be quickly advanced to preclinical and clinical tests for COVID-19.
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1MPro ), we have designed and synthesized a series of SC2MPro inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active-site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound, MPI3, has as a Ki value of 8.3 nM. Crystallographic analyses of SC2MPro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5 μM and A549/ACE2 cells at 0.16-0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with ultra-high antiviral potency.
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1MPro ), we have designed and synthesized a series of SC2MPro inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active-site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound, MPI3, has as a Ki value of 8.3 nM. Crystallographic analyses of SC2MPro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5 μM and A549/ACE2 cells at 0.16-0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with ultra-high antiviral potency.The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1MPro ), we have designed and synthesized a series of SC2MPro inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active-site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound, MPI3, has as a Ki value of 8.3 nM. Crystallographic analyses of SC2MPro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5 μM and A549/ACE2 cells at 0.16-0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with ultra-high antiviral potency.
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1M ), we have designed and synthesized a series of SC2M inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2M active-site cysteine C145. All inhibitors display high potency with K values at or below 100 nM. The most potent compound, MPI3, has as a K value of 8.3 nM. Crystallographic analyses of SC2M bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5 μM and A549/ACE2 cells at 0.16-0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2M inhibitors with ultra-high antiviral potency.
The COVID‐19 pathogen, SARS‐CoV‐2, requires its main protease (SC2M Pro ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID‐19 treatment option. Guided by previous medicinal chemistry studies about SARS‐CoV‐1 main protease (SC1M Pro ), we have designed and synthesized a series of SC2M Pro inhibitors that contain β‐(S‐2‐oxopyrrolidin‐3‐yl)‐alaninal (Opal) for the formation of a reversible covalent bond with the SC2M Pro active‐site cysteine C145. All inhibitors display high potency with K i values at or below 100 nM. The most potent compound, MPI3, has as a K i value of 8.3 nM. Crystallographic analyses of SC2M Pro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS‐CoV‐2‐induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS‐CoV‐2‐induced cytopathogenic effect in Vero E6 cells at 2.5–5 μM and A549/ACE2 cells at 0.16–0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID‐19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2M Pro inhibitors with ultra‐high antiviral potency.
The COVID‐19 pathogen, SARS‐CoV‐2, requires its main protease (SC2MPro) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID‐19 treatment option. Guided by previous medicinal chemistry studies about SARS‐CoV‐1 main protease (SC1MPro), we have designed and synthesized a series of SC2MPro inhibitors that contain β‐(S‐2‐oxopyrrolidin‐3‐yl)‐alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active‐site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound, MPI3, has as a Ki value of 8.3 nM. Crystallographic analyses of SC2MPro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS‐CoV‐2‐induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS‐CoV‐2‐induced cytopathogenic effect in Vero E6 cells at 2.5–5 μM and A549/ACE2 cells at 0.16–0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID‐19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with ultra‐high antiviral potency. Small but strong: A series of SARS‐CoV‐2 MPro covalent inhibitors exhibit excellent activity. Protein crystallography analysis and a live virus‐based microneutralization assay found two of the most potent anti‐SARS‐CoV‐2 small molecules so far. Due to the urgent matter of the COVID‐19 pandemic, these two inhibitors could be quickly advanced to preclinical and clinical tests for COVID‐19.
Author Sheng, Yan J.
Kratch, Kaci C.
Yang, Kai S.
Xu, Shiqing
Ma, Yuying
Ma, Xinyu R.
Alugubelli, Yugendar R.
Vatansever, Erol C.
Liu, Jin
Geng, Zhi Z.
Blankenship, Lauren R.
Sankaran, Banumathi
Liu, Wenshe Ray
Tseng, Chien‐Te K.
Li, Pingwei
Ward, Hannah E.
Zhao, Baoyu
Hsu, Jason C.
Hayatshahi, Hamed S.
Scott, Danielle A.
Drelich, Aleksandra K.
Fierke, Carol A.
AuthorAffiliation f Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA
b Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
d Department of Biochemistry and Biophysics, Texas A&M University College Station, TX 77843, USA
e Department of Pharmaceutical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
g Institute of Biosciences and Technology and Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, TX 77030, USA
c Molecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
a Department of Chemistry, Texas A&M University College Station, TX 77843-3255, USA
AuthorAffiliation_xml – name: d Department of Biochemistry and Biophysics, Texas A&M University College Station, TX 77843, USA
– name: a Department of Chemistry, Texas A&M University College Station, TX 77843-3255, USA
– name: g Institute of Biosciences and Technology and Department of Translational Medical Sciences, College of Medicine, Texas A&M University, Houston, TX 77030, USA
– name: e Department of Pharmaceutical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
– name: b Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
– name: c Molecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
– name: f Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA
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  givenname: Kai S.
  surname: Yang
  fullname: Yang, Kai S.
  organization: Texas A&M University
– sequence: 2
  givenname: Xinyu R.
  surname: Ma
  fullname: Ma, Xinyu R.
  organization: Texas A&M University
– sequence: 3
  givenname: Yuying
  surname: Ma
  fullname: Ma, Yuying
  organization: Texas A&M University
– sequence: 4
  givenname: Yugendar R.
  surname: Alugubelli
  fullname: Alugubelli, Yugendar R.
  organization: Texas A&M University
– sequence: 5
  givenname: Danielle A.
  surname: Scott
  fullname: Scott, Danielle A.
  organization: Texas A&M University
– sequence: 6
  givenname: Erol C.
  surname: Vatansever
  fullname: Vatansever, Erol C.
  organization: Texas A&M University
– sequence: 7
  givenname: Aleksandra K.
  surname: Drelich
  fullname: Drelich, Aleksandra K.
  organization: University of Texas Medical Branch
– sequence: 8
  givenname: Banumathi
  surname: Sankaran
  fullname: Sankaran, Banumathi
  organization: Lawrence Berkeley National Laboratory
– sequence: 9
  givenname: Zhi Z.
  surname: Geng
  fullname: Geng, Zhi Z.
  organization: Texas A&M University
– sequence: 10
  givenname: Lauren R.
  surname: Blankenship
  fullname: Blankenship, Lauren R.
  organization: Texas A&M University
– sequence: 11
  givenname: Hannah E.
  surname: Ward
  fullname: Ward, Hannah E.
  organization: Texas A&M University
– sequence: 12
  givenname: Yan J.
  surname: Sheng
  fullname: Sheng, Yan J.
  organization: Texas A&M University
– sequence: 13
  givenname: Jason C.
  surname: Hsu
  fullname: Hsu, Jason C.
  organization: University of Texas Medical Branch
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  givenname: Kaci C.
  surname: Kratch
  fullname: Kratch, Kaci C.
  organization: Texas A&M University
– sequence: 15
  givenname: Baoyu
  surname: Zhao
  fullname: Zhao, Baoyu
  organization: Texas A&M University
– sequence: 16
  givenname: Hamed S.
  surname: Hayatshahi
  fullname: Hayatshahi, Hamed S.
  organization: UNT Health Science Center
– sequence: 17
  givenname: Jin
  orcidid: 0000-0002-7078-6534
  surname: Liu
  fullname: Liu, Jin
  organization: UNT Health Science Center
– sequence: 18
  givenname: Pingwei
  surname: Li
  fullname: Li, Pingwei
  organization: Texas A&M University
– sequence: 19
  givenname: Carol A.
  surname: Fierke
  fullname: Fierke, Carol A.
  email: cafierke@tamu.edu
  organization: Texas A&M University
– sequence: 20
  givenname: Chien‐Te K.
  surname: Tseng
  fullname: Tseng, Chien‐Te K.
  email: sktseng@utmb.edu
  organization: University of Texas Medical Branch
– sequence: 21
  givenname: Shiqing
  surname: Xu
  fullname: Xu, Shiqing
  email: shiqing.xu@tamu.edu
  organization: Texas A&M University
– sequence: 22
  givenname: Wenshe Ray
  surname: Liu
  fullname: Liu, Wenshe Ray
  email: wliu@chem.tamu.edu
  organization: Texas A&M University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33283984$$D View this record in MEDLINE/PubMed
https://www.osti.gov/servlets/purl/1837373$$D View this record in Osti.gov
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Keywords COVID-19
3C-like protease
antivirals
reversible covalent inhibitors
SARS-CoV-2
EFFICACY
main protease
IDENTIFICATION
CORONAVIRUS
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A previous version of this manuscript has been deposited on a preprint server
https://doi.org/10.1101/2020.07.28.223784
These authors contributed equally to the paper.
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Snippet The COVID‐19 pathogen, SARS‐CoV‐2, requires its main protease (SC2MPro) to digest two of its translated long polypeptides to form a number of mature proteins...
The COVID‐19 pathogen, SARS‐CoV‐2, requires its main protease (SC2M Pro ) to digest two of its translated long polypeptides to form a number of mature proteins...
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M(Pro)) to digest two of its translated long polypeptides to form a number of mature proteins...
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M ) to digest two of its translated long polypeptides to form a number of mature proteins...
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro ) to digest two of its translated long polypeptides to form a number of mature proteins...
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M Pro ) to digest two of its translated long polypeptides to form a number of mature proteins...
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proquest
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StartPage 942
SubjectTerms 3C-like protease
60 APPLIED LIFE SCIENCES
A549 Cells
ACE2
Alanine - analogs & derivatives
Alanine - metabolism
Alanine - pharmacology
Angiotensin-converting enzyme 2
Animals
Antiviral Agents - chemical synthesis
Antiviral Agents - metabolism
Antiviral Agents - pharmacology
Antiviral drugs
antivirals
Catalytic Domain
Chemical bonds
Chemistry, Medicinal
Chlorocebus aethiops
Coronavirus 3C Proteases - antagonists & inhibitors
Coronavirus 3C Proteases - chemistry
Coronavirus 3C Proteases - metabolism
Covalent bonds
COVID-19
Crystallography
Cysteine - chemistry
Cysteine Proteinase Inhibitors - chemical synthesis
Cysteine Proteinase Inhibitors - metabolism
Cysteine Proteinase Inhibitors - pharmacology
Humans
Life Sciences & Biomedicine
main protease
Microbial Sensitivity Tests
Pathogenesis
Pharmacology & Pharmacy
Polypeptides
Protease
Protease inhibitors
Protein Binding
Proteinase inhibitors
Proteolysis
Pyrrolidinones - chemical synthesis
Pyrrolidinones - metabolism
Pyrrolidinones - pharmacology
reversible covalent inhibitors
SARS-CoV-2
SARS-CoV-2 - drug effects
SARS-CoV-2 - enzymology
Science & Technology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Vero Cells
Viral diseases
Viruses
Title A Quick Route to Multiple Highly Potent SARS‐CoV‐2 Main Protease Inhibitors
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcmdc.202000924
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Volume 16
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