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

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; Asn(40)-Thr(47), Val(57)-Pro(59), Gly(69)-Ser(72), Cys(77)-Pro(84), Lys(93)-Tyr(96). In addition, polar contacts between nsp16 and Zyesami are Asn(299)-Ser(440), Val(297)-Asn(443), Gly(149)-Tyr(437), Gln(159)-Lys(430), Asn(178)-Arg(429), Ser(146)-Arg(429), Ser(146)-Arg(429), Lys(147)-Arg(429), Asr(221)-Thr(422), Lys(183)-Asp(423), Lys(183)-Asp(423), and Gln(219)-Asp(423) 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 SARS-CoV nsp10/16 complex.

Automated summary

The study found that Zyesami has inhibitory effects on the SARS-CoV-2 nsp10/nsp16 complex, which may be used as a drug for COVID-19 treatment.