OpenLB
Open Library of Bioscience
Advanced Search
Viruses
10 30, 2023;15 (11):

Covalent Inhibitors from Saudi Medicinal Plants Target RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2.

Ahmed H Bakheit, Quaiser Saquib, Sarfaraz Ahmed, Sabiha M Ansari, Abdullah M Al-Salem, Abdulaziz A Al-Khedhairy
Author Information
  1. Ahmed H Bakheit: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ORCID
  2. Quaiser Saquib: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. ORCID
  3. Sarfaraz Ahmed: Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  4. Sabiha M Ansari: Botany & Microbiology Department, College of Sciences, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  5. Abdullah M Al-Salem: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
  6. Abdulaziz A Al-Khedhairy: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
PMID: 38005857 DOI: 10.3390/v15112175

Abstract

COVID-19, a disease caused by SARS-CoV-2, has caused a huge loss of human life, and the number of deaths is still continuing. Despite the lack of repurposed drugs and vaccines, the search for potential small molecules to inhibit SARS-CoV-2 is in demand. Hence, we relied on the drug-like characters of ten phytochemicals (compounds -) that were previously isolated and purified by our research team from Saudi medicinal plants. We computationally evaluated the inhibition of RNA-dependent RNA polymerase (RdRp) by compounds -. Non-covalent (reversible) docking of compounds - with RdRp led to the formation of a hydrogen bond with template primer nucleotides (A and U) and key amino acid residues (ASP623, LYS545, ARG555, ASN691, SER682, and ARG553) in its active pocket. Covalent (irreversible) docking revealed that compounds , , and exhibited their irreversible nature of binding with CYS813, a crucial amino acid in the palm domain of RdRP. Molecular dynamic (MD) simulation analysis by RMSD, RMSF, and Rg parameters affirmed that RdRP complexes with compounds , , and were stable and showed less deviation. Our data provide novel information on compounds , , and that demonstrated their non-nucleoside and irreversible interaction capabilities to inhibit RdRp and shed new scaffolds as antivirals against SARS-CoV-2.

Keywords

COVID-19 MD simulation RdRp SARS-CoV-2 docking medicinal plants phytochemicals

References

J Pharm Anal. 2020 Apr;10(2):102-108 [PMID: 32282863]
PLoS One. 2021 May 13;16(5):e0251801 [PMID: 33984041]
Microb Pathog. 2022 Jul;168:105512 [PMID: 35381324]
Bioorg Med Chem. 2023 Feb 15;80:117179 [PMID: 36716583]
Cell Rep. 2021 Dec 28;37(13):110167 [PMID: 34919800]
Future Med Chem. 2022 Mar;14(6):393-405 [PMID: 35220726]
Nature. 2020 Mar;579(7798):270-273 [PMID: 32015507]
iScience. 2020 Dec 26;24(1):101992 [PMID: 33490902]
J Infect Public Health. 2021 May;14(5):601-610 [PMID: 33848890]
Antimicrob Agents Chemother. 2014 Jun;58(6):3485-95 [PMID: 24733465]
Antiviral Res. 2020 Jun;178:104792 [PMID: 32272173]
Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):1274-1279 [PMID: 29358381]
Antimicrob Agents Chemother. 2005 Mar;49(3):981-6 [PMID: 15728892]
J Chem Inf Model. 2018 Jul 23;58(7):1441-1458 [PMID: 29890081]
Phytomed Plus. 2021 Feb;1(1):100002 [PMID: 35403083]
J Phys Chem B. 2016 Apr 21;120(15):3692-8 [PMID: 27031562]
Lancet Rheumatol. 2020 May;2(5):e255-e256 [PMID: 32368737]
Cell. 2021 Jun 10;184(12):3086-3108 [PMID: 34087172]
Molecules. 2020 Aug 07;25(16): [PMID: 32784576]
Front Immunol. 2022 Apr 04;13:855496 [PMID: 35444647]
Nat Rev Immunol. 2021 Jun;21(6):382-393 [PMID: 33875867]
Clin Microbiol Rev. 2016 Jul;29(3):695-747 [PMID: 27281742]
J Infect Public Health. 2023 Apr;16(4):501-519 [PMID: 36801630]
J Comput Chem. 2010 Mar;31(4):671-90 [PMID: 19575467]
Comput Biol Med. 2022 Dec;151(Pt A):106284 [PMID: 36370580]
Arab J Chem. 2023 Aug;16(8):104939 [PMID: 37193561]
Comput Biol Med. 2022 Jun;145:105468 [PMID: 35390745]
Lancet Infect Dis. 2020 Aug;20(8):911-919 [PMID: 32353347]
Molecules. 2022 Dec 25;28(1): [PMID: 36615354]
Biosci Trends. 2020 Mar 16;14(1):69-71 [PMID: 31996494]
Cytokine Growth Factor Rev. 2020 Jun;53:66-70 [PMID: 32418715]
Food Chem Toxicol. 2021 Feb;148:111966 [PMID: 33412235]
Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221142793 [PMID: 36442514]
J Comput Chem. 2005 Dec;26(16):1781-802 [PMID: 16222654]
Heliyon. 2023 May;9(5):e15860 [PMID: 37153407]
Comput Biol Med. 2023 May;157:106785 [PMID: 36931201]
Genomics. 2021 Jan;113(1 Pt 2):1129-1140 [PMID: 33189776]
Proteins. 2009 Apr;75(1):187-205 [PMID: 18814299]
ChemMedChem. 2022 Aug 17;17(16):e202200278 [PMID: 35726731]
Acta Pharm Sin B. 2021 Jan;11(1):237-245 [PMID: 32895623]
Proc Natl Acad Sci U S A. 2021 Feb 16;118(7): [PMID: 33526596]
J Infect Public Health. 2023 Jan;16(1):42-54 [PMID: 36470006]
Protein Eng Des Sel. 2016 Feb;29(2):65-76 [PMID: 26647400]
J Comput Chem. 2008 Aug;29(11):1859-65 [PMID: 18351591]
Sci Rep. 2020 Nov 30;10(1):20808 [PMID: 33257760]
Sci Rep. 2022 Jun 28;12(1):10896 [PMID: 35764663]
Eur J Pharmacol. 2021 Jun 15;901:174082 [PMID: 33823185]
J Biomol Struct Dyn. 2021 Aug;39(12):4522-4535 [PMID: 32552534]
Virus Res. 2020 Jul 15;284:197989 [PMID: 32360300]
Adv Virus Res. 2019;105:93-116 [PMID: 31522710]
J Am Chem Soc. 2020 Feb 19;142(7):3392-3400 [PMID: 32009391]
J Biomol Struct Dyn. 2022 Feb;40(3):1084-1100 [PMID: 32940134]
Science. 2020 May 15;368(6492):779-782 [PMID: 32277040]
SLAS Discov. 2017 Jan;22(1):3-20 [PMID: 27703080]
Front Microbiol. 2022 Jul 22;13:926929 [PMID: 35935185]
Open Forum Infect Dis. 2022 Jan 19;9(3):ofac008 [PMID: 35165657]
Biomed Pharmacother. 2021 Feb;134:111143 [PMID: 33360048]
Rev Med Virol. 2006 Jan-Feb;16(1):37-48 [PMID: 16287208]
Antiviral Res. 2018 Dec;160:109-117 [PMID: 30316915]
Science. 2020 Jun 26;368(6498):1499-1504 [PMID: 32358203]
J Med Chem. 2022 Oct 13;65(19):12500-12534 [PMID: 36169610]
mBio. 2022 Apr 26;13(2):e0297921 [PMID: 35352979]
J Med Chem. 2014 Aug 14;57(15):6668-78 [PMID: 25019388]
Antiviral Res. 2007 May;74(2):92-101 [PMID: 16730806]
Wiley Interdiscip Rev RNA. 2013 Jul-Aug;4(4):351-67 [PMID: 23606593]
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463 [PMID: 28769016]
Phytomedicine. 2021 May;85:153317 [PMID: 32943302]
J Comput Chem. 2012 Dec 5;33(31):2451-68 [PMID: 22821581]
J Comput Aided Mol Des. 2012 Jun;26(6):775-86 [PMID: 22566074]
Pharmaceuticals (Basel). 2023 Apr 28;16(5): [PMID: 37242447]
J Chem Inf Model. 2007 Jan-Feb;47(1):122-33 [PMID: 17238257]
ACS Cent Sci. 2021 Jan 27;7(1):164-174 [PMID: 33527086]
Eur J Med Chem. 2023 Jun 5;254:115376 [PMID: 37080108]
Comput Biol Med. 2023 Feb;153:106449 [PMID: 36586228]
Heliyon. 2020 Jul 23;6(7):e04502 [PMID: 32754651]
ACS Pharmacol Transl Sci. 2022 May 17;5(6):445-447 [PMID: 35702394]
Cell. 2020 Apr 16;181(2):271-280.e8 [PMID: 32142651]
Methods Mol Biol. 2015;1282:1-23 [PMID: 25720466]
Bioorg Med Chem. 2021 Oct 1;47:116386 [PMID: 34509863]
Toxicol In Vitro. 2019 Feb;54:338-344 [PMID: 30385350]
Nat Med. 2020 May;26(5):681-687 [PMID: 32327758]
J Biol Chem. 2020 May 15;295(20):6785-6797 [PMID: 32284326]
Phytomedicine. 2023 Jun;114:154796 [PMID: 37037086]

Grants

  1. 5-21-01-001-0025/This research was funded by King Abdulaziz City for Science and Technology (KACST) via the Fast Track Funding Path for COVID-19 Research Projects, grant number 5-21-01-001-0025.

MeSH Term

Amino Acids
Antiviral Agents
Molecular Docking Simulation
Molecular Dynamics Simulation
Plants, Medicinal
RNA-Dependent RNA Polymerase
SARS-CoV-2
Saudi Arabia

Chemicals

Amino Acids
Antiviral Agents
RNA-Dependent RNA Polymerase
Journal Article

Word Cloud

Similar Articles

Cited By