دورية أكاديمية
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Remdesivir Strongly Binds to Both RNA-Dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations.

التفاصيل البيبلوغرافية
العنوان: Remdesivir Strongly Binds to Both RNA-Dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations.
المؤلفون: Nguyen HL; Life Science Lab, Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City 700000, Vietnam., Thai NQ; Life Science Lab, Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City 700000, Vietnam.; Dong Thap University, 783 Pham Huu Lau Street, Ward 6, Cao Lanh City 870000, Dong Thap, Vietnam., Truong DT; Life Science Lab, Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City 700000, Vietnam., Li MS; Institute of Physics, Polish Academy of Sciences, al. Lotnikow 32/46, Warsaw 02-668, Poland.
المصدر: The journal of physical chemistry. B [J Phys Chem B] 2020 Dec 17; Vol. 124 (50), pp. 11337-11348. Date of Electronic Publication: 2020 Dec 02.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101157530 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5207 (Electronic) Linking ISSN: 15205207 NLM ISO Abbreviation: J Phys Chem B Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, c1997-
مواضيع طبية MeSH: Adenosine Monophosphate/*analogs & derivatives , Alanine/*analogs & derivatives , Antiviral Agents/*metabolism , Coronavirus 3C Proteases/*metabolism , RNA-Dependent RNA Polymerase/*metabolism , SARS-CoV-2/*metabolism, Adenosine Monophosphate/metabolism ; Alanine/metabolism ; Algorithms ; Humans ; Hydrogen Bonding ; Models, Molecular ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Binding ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; Static Electricity
مستخلص: The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) has caused a global COVID-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for COVID-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to COVID-19 patients in many countries. A recent experiment showed that remdesivir binds to SARS-CoV-2 with an inhibition constant of μM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics, and umbrella sampling, we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that remdesivir binds to Mpro slightly weaker than to RdRp, and the corresponding inhibition constants, consistent with the experiment, fall to the μM range. The binding mechanisms of remdesivir to two targets differ in that the electrostatic interaction is the main force in stabilizing the RdRp-remdesivir complex, while the van der Waals interaction dominates in the Mpro-remdesivir case. Our result indicates that remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating COVID-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease.
References: Nature. 2020 Mar;579(7798):270-273. (PMID: 32015507)
Protein Cell. 2010 Jan;1(1):59-74. (PMID: 21203998)
Annu Rev Biophys Biomol Struct. 2000;29:291-325. (PMID: 10940251)
Phys Rev Lett. 2007 Aug 10;99(6):068101. (PMID: 17930869)
J Med Virol. 2020 May;92(5):476-478. (PMID: 32056235)
mBio. 2018 Mar 6;9(2):. (PMID: 29511076)
N Engl J Med. 2020 Jun 11;382(24):2327-2336. (PMID: 32275812)
Proteins. 2010 Jun;78(8):1950-8. (PMID: 20408171)
J Phys Chem B. 2018 May 3;122(17):4693-4699. (PMID: 29630379)
J Comput Chem. 2004 Jul 15;25(9):1157-74. (PMID: 15116359)
Protein Eng. 1994 Mar;7(3):385-91. (PMID: 8177887)
J Med Virol. 2020 Apr;92(4):455-459. (PMID: 31994738)
J Mol Graph Model. 1999 Feb;17(1):57-61. (PMID: 10660911)
Sci Rep. 2016 Mar 07;6:22677. (PMID: 26948040)
J Virol. 1996 Jul;70(7):4773-7. (PMID: 8676505)
Cell Res. 2020 Mar;30(3):269-271. (PMID: 32020029)
J Chem Theory Comput. 2017 Jan 10;13(1):210-222. (PMID: 27997169)
ACS Cent Sci. 2020 Mar 25;6(3):315-331. (PMID: 32226821)
Sci Transl Med. 2017 Jun 28;9(396):. (PMID: 28659436)
Int J Antimicrob Agents. 2020 Mar;55(3):105924. (PMID: 32081636)
Nat Rev Drug Discov. 2016 May;15(5):327-47. (PMID: 26868298)
J Chem Phys. 2010 Jul 28;133(4):044114. (PMID: 20687640)
J Gen Virol. 2000 Apr;81(Pt 4):853-79. (PMID: 10725411)
J Mol Biol. 1982 May 5;157(1):105-32. (PMID: 7108955)
J Biomol Struct Dyn. 2021 Aug;39(13):4701-4714. (PMID: 32568620)
JAMA. 2020 Apr 28;323(16):1559-1560. (PMID: 32250408)
Curr Opin Struct Biol. 2018 Apr;49:1-10. (PMID: 29132080)
BMC Res Notes. 2012 Jul 23;5:367. (PMID: 22824207)
Nat Commun. 2019 May 28;10(1):2342. (PMID: 31138817)
J Comput Chem. 2002 Dec;23(16):1623-41. (PMID: 12395429)
Expert Opin Drug Discov. 2015 May;10(5):449-61. (PMID: 25835573)
J Comput Chem. 2010 Jan 30;31(2):455-61. (PMID: 19499576)
JAMA. 2020 Apr 7;323(13):1245-1246. (PMID: 32074258)
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13190-5. (PMID: 14585926)
Biochemistry. 2020 May 12;59(18):1769-1779. (PMID: 32293875)
Nature. 2016 Mar 17;531(7594):381-5. (PMID: 26934220)
Science. 2020 Apr 24;368(6489):409-412. (PMID: 32198291)
Science. 2020 May 15;368(6492):779-782. (PMID: 32277040)
J Med Virol. 2020 Apr;92(4):418-423. (PMID: 31967327)
EMBO J. 2002 Jul 1;21(13):3213-24. (PMID: 12093723)
J Travel Med. 2020 Mar 13;27(2):. (PMID: 32052846)
Nat Microbiol. 2020 Apr;5(4):536-544. (PMID: 32123347)
J Biomol Struct Dyn. 2021 Jun;39(9):3409-3418. (PMID: 32306836)
Nat Rev Microbiol. 2019 Mar;17(3):181-192. (PMID: 30531947)
Science. 2020 Jun 26;368(6498):1499-1504. (PMID: 32358203)
J Chem Phys. 2004 Apr 1;120(13):5946-61. (PMID: 15267476)
J Virol. 2008 Mar;82(5):2515-27. (PMID: 18094151)
J Chem Inf Model. 2011 Sep 26;51(9):2266-76. (PMID: 21834591)
J Chem Inf Model. 2015 Dec 28;55(12):2731-8. (PMID: 26595261)
Nature. 2020 Jun;582(7811):289-293. (PMID: 32272481)
Nat Med. 2005 Aug;11(8):875-9. (PMID: 16007097)
Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2006-2011. (PMID: 32141569)
J Chem Inf Model. 2011 Oct 24;51(10):2778-86. (PMID: 21919503)
Phys Rev Lett. 1986 Mar 3;56(9):930-933. (PMID: 10033323)
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3658-61. (PMID: 11274384)
Lancet. 2020 Mar 28;395(10229):1033-1034. (PMID: 32192578)
Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):E3900-9. (PMID: 25197083)
Int J Mol Sci. 2020 Apr 28;21(9):. (PMID: 32353978)
J Chem Phys. 2007 Jan 7;126(1):014101. (PMID: 17212484)
J Phys Chem B. 2020 Aug 27;124(34):7336-7347. (PMID: 32790406)
J Biomol Struct Dyn. 2021 Jun;39(9):3204-3212. (PMID: 32338164)
Curr Protoc Bioinformatics. 2006 Oct;Chapter 5:Unit-5.6. (PMID: 18428767)
المشرفين على المادة: 0 (Antiviral Agents)
3QKI37EEHE (remdesivir)
415SHH325A (Adenosine Monophosphate)
EC 2.7.7.48 (RNA-Dependent RNA Polymerase)
EC 3.4.22.28 (Coronavirus 3C Proteases)
OF5P57N2ZX (Alanine)
تواريخ الأحداث: Date Created: 20201202 Date Completed: 20210107 Latest Revision: 20230829
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7724981
DOI: 10.1021/acs.jpcb.0c07312
PMID: 33264025
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-5207
DOI:10.1021/acs.jpcb.0c07312