* Corresponding Author
Potential of Favipiravir Analogs as SARS-CoV-2 RdRp Inhibitors: Synthesis and In Silico Studies
https://doi.org/10.22146/ijc.98538 Anita Alni(1*), Angela Lokitha(2), Yusuf Eka Maulana(3), Elvira Hermawati(4), Ade Danova(5)
(1) Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia
(2) Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia
(3) Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia
(4) Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia
(5) Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No. 10, Bandung 40132, Indonesia
(*) Corresponding Author
Abstract
The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for causing the lethal infectious disease known as COVID-19. The RNA-dependent RNA polymerase (RdRp) is a pivotal component that facilitates the translation of viral RNA into viral proteins. Therefore, our study aimed to synthesize new inhibitors from favipiravir (FVP) analogs by modifying the hydrophobicity through a nucleophilic aromatic substitution at the C-6 position of the pyrazine ring with alkoxy groups under acidic conditions. Moreover, the synthesized FVP analogs were investigated for their antiviral potency against SARS-CoV-2 RdRp through in silico studies. Five FVP analogs (3–7), including four known (3, 4, 5, 7) and one new (6), were successfully synthesized with yields ranging from 2.3 to 32.7%. All favipiravir analogs could be drug-likeness with inactive hepatotoxicity and carcinogenicity. The docking study showed that compound 5 exhibited a strong binding affinity with a binding score of −7.00 kcal/mol by interacting with the catalytic site residues of Asp618 and Asp760 of SARS-CoV-2 RdRp. Furthermore, the molecular dynamics simulation revealed that the compound 5 was stable, as indicated by RMSD, Rg, solute H-bonds, RMSF, and binding energy calculations. Thus, these results suggest that the FVP-RTP analog (5) may have antiviral potency by targeting SARS-CoV-2 RdRp.
Keywords
References
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DOI: https://doi.org/10.22146/ijc.98538
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