PMID- 35991504
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230831
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 7
IP  - 33
DP  - 2022 Aug 23
TI  - Small Molecules Targeting SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain.
PG  - 28779-28789
LID - 10.1021/acsomega.2c00844 [doi]
AB  - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the 
      coronavirus disease 2019 (COVID-19) pandemic. Several variants of SARS-CoV-2 have 
      emerged worldwide. These variants show different transmissibility infectivity due 
      to mutations in the viral spike (S) glycoprotein that interacts with the human 
      angiotensin-converting enzyme 2 (hACE2) receptor and facilitates viral entry into 
      target cells. Despite the effective SARS-CoV-2 vaccines, we still need to 
      identify selective antivirals, and the S glycoprotein is a key target to 
      neutralize the virus. We hypothesize that small molecules could disrupt the 
      interaction of S glycoprotein with hACE2 and inhibit viral entry. We analyzed the 
      S glycoprotein-hACE2 complex structure (PDB: 7DF4) and created models for 
      different viral variants using visual molecular dynamics (VMD) and molecular 
      operating environment (MOE) programs. Moreover, we started the hits search by 
      performing structure-based molecular docking virtual screening of commercially 
      available small molecules against S glycoprotein models using OEDocking 
      FRED-4.0.0.0 software. The FRED-4.0.0.0 Chemguass4 scoring function was used to 
      rank the small molecules based on their affinities. The best candidate compounds 
      were purchased and tested using a standard SARS-CoV-2 pseudotyped cell-based 
      bioassay to investigate their antiviral activity. Three of these compounds, alone 
      or in combination, showed antiviral selectivity. These small molecules may lead 
      to an effective antiviral treatment or serve as probes to better understand the 
      biology of SARS-CoV-2.
CI  - (c) 2022 The Authors. Published by American Chemical Society.
FAU - Rodriguez, Yoel
AU  - Rodriguez Y
AUID- ORCID: 0000-0002-7334-7828
AD  - Department of Natural Sciences, Hostos Community College of The City University 
      of New York, 500 Grand Concourse, Bronx, New York, New York 10451, United States.
AD  - Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, 
      1425 Madison Avenue, New York, New York 10029, United States.
FAU - Cardoze, Scarlet Martinez
AU  - Cardoze SM
AD  - Department of Natural Sciences, Hostos Community College of The City University 
      of New York, 500 Grand Concourse, Bronx, New York, New York 10451, United States.
FAU - Obineche, Onyinyechi W
AU  - Obineche OW
AD  - Department of Natural Sciences, Hostos Community College of The City University 
      of New York, 500 Grand Concourse, Bronx, New York, New York 10451, United States.
FAU - Melo, Claudia
AU  - Melo C
AUID- ORCID: 0000-0003-2663-1196
AD  - Department of Science, Borough of Manhattan Community College of The City 
      University of New York, 199 Chambers St, New York, New York 10007, United States.
AD  - Brooklyn College of The City University of New York, 2900 Bedford Avenue, New 
      York, New York 11210, United States.
FAU - Persaud, Ashanna
AU  - Persaud A
AD  - Department of Science, Borough of Manhattan Community College of The City 
      University of New York, 199 Chambers St, New York, New York 10007, United States.
FAU - Fernandez Romero, Jose A
AU  - Fernandez Romero JA
AD  - Department of Science, Borough of Manhattan Community College of The City 
      University of New York, 199 Chambers St, New York, New York 10007, United States.
AD  - Center for Biomedical Research, The Population Council, 1230 York Avenue, New 
      York, New York 10065, United States.
LA  - eng
GR  - T34 GM008078/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20220809
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC9380817
COIS- The authors declare no competing financial interest.
EDAT- 2022/08/23 06:00
MHDA- 2022/08/23 06:01
PMCR- 2022/08/09
CRDT- 2022/08/22 04:12
PHST- 2022/02/10 00:00 [received]
PHST- 2022/07/06 00:00 [accepted]
PHST- 2022/08/22 04:12 [entrez]
PHST- 2022/08/23 06:00 [pubmed]
PHST- 2022/08/23 06:01 [medline]
PHST- 2022/08/09 00:00 [pmc-release]
AID - 10.1021/acsomega.2c00844 [doi]
PST - epublish
SO  - ACS Omega. 2022 Aug 9;7(33):28779-28789. doi: 10.1021/acsomega.2c00844. 
      eCollection 2022 Aug 23.