Molecular Interactions of Zyesami with the SARS-CoV-2 nsp10/nsp16
Protein Complex

Sultan   F.   Alnomasy; Bader   S.   Alotaibi; Ziyad   M.   Aldosari; Ahmed   H.   Mujamammi; Ahmad      Alzamami; Pragya      Anand; Yusuf      Akhter; Farhan   R.   Khan; Mohammad   R.   Hasan

doi:10.2174/1386207325666220816141028

Abstract

Background: SARS-CoV-2 emerged in late 2019 and caused COVID-19. Patients treated with Zyesami were found to have a 3-fold decrease in respiratory failure and improved clinical outcomes. It was reported that Zyesami inhibits RNA replication of SARS-CoV-2, including several non-structural proteins essential in viral RNA replication. SARS-CoV-2 is a distinctive virus that requires nsp10 and nsp16 for its methyltransferases activity which is crucial for RNA stability and protein synthesis.

Objective: We aimed the in silico determination of inhibitory consequences of Zyesami on the SARS-CoV-2 nsp10/nsp16 complex. Targeting SARS-CoV-2 nsp10/ nsp16 protein complex may be used to develop a drug against COVID-19.

Methods: I-TASSER was used for secondary structure prediction of Zyesami. CABS-dock was used to model Zyesami with SARS-CoV-2 nsp16 interaction. The docked complex was visualized using PyMol. The quality of the docking model was checked by using ProQdock.

Results: The 3D structure of SARS-CoV 2, nsp10/nsp16 showed that essential interactions exist between nsp10 and nsp16. Significant contact areas of Zyesami exist across amino acid residues of nsp10; Asn⁴⁰-Thr⁴⁷, Val57-Pro⁵⁹, Gly⁶⁹-Ser⁷², Cys⁷⁷-Pro⁸⁴, Lys⁹³-Tyr⁹⁶. In addition, polar contacts between nsp16 and Zyesami are Asn²⁹⁹-Ser⁴⁴⁰, Val²⁹⁷-Asn⁴⁴³, Gly¹⁴⁹-Tyr⁴³⁷, Gln¹⁵⁹-Lys⁴³⁰, Asn¹⁷⁸- Arg⁴²⁹, Ser¹⁴⁶-Arg⁴²⁹, Ser¹⁴⁶-Arg⁴²⁹, Lys¹⁴⁷-Arg⁴²⁹, Asr²²¹-Thr⁴²², Lys¹⁸³-Asp⁴²³, Lys¹⁸³-Asp⁴²³, and Gln²¹⁹-Asp⁴²³ the residues are shown of nsp16 and Zyesami respectively.

Conclusion: The structural bioinformatics analyses have indicated the potential binding specificity of Zyesami and nsp16. Data predict how the initial binding of Zyesami with nsp10 and nsp16 may occur. Moreover, this binding could significantly inhibit the 2 -O-MTase activity of the SARSCoV nsp10/16 complex.

Keywords: COVID-19, SARS-CoV-2, Microbiology, Zyesami, Coronavirus, nsp16, nsp10

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DOI https://dx.doi.org/10.2174/1386207325666220816141028	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

Combinatorial Chemistry & High Throughput Screening

Molecular Interactions of Zyesami with the SARS-CoV-2 nsp10/nsp16 Protein Complex

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