Adamantane as the potential candidate for conjugation along with natural compounds as a potential drug for Sars-CoV-2

• Author Details:   
• Amar Prakash Garg ^*
• Rahul Dev Ambedkar

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We need to develop antiviral drugs against Sars-CoV-2 main protease (M^pro) because it is essential for viral replication. The M^pro enzyme has separate catalytic and dimerisation domains and operates as a homodimer. Being peptidic in nature, Cys145 and His41, two catalytic residues, are essential for inhibition. Current inhibitors are GC-376, PF-00835231. Non-peptidic inhibitors like Wu04, R, and S-216722 are also promising candidates as less harmful substitutes. FDA-approved medications like Remdesivir and Nirmatrelvir have drawbacks that include decreased efficacy and interactions. Non-peptidic inhibitors, such as AF 399/40713777 and AI-942/42301830, exhibit modest M^pro inhibition. The use of virtual screening, molecular dynamics coupled with computer-aided drug design (CADD) has made it possible to find 17 new M^pro inhibitors. Furthermore, substantial M^pro inhibition has been demonstrated by natural compounds such flavonoids and glycosides, suggesting their potential as therapeutic agents. In preclinical settings, AMA derivatives—especially 3F4—show notable antiviral activity and decreased toxicity among new drugs. It suggests potential of combinatorial therapy and the significance of various inhibitor types for efficient Sars-CoV-2.

Keywords: Sars-CoV-2, M^pro, Adamantane. Remdesivir, Nirmatrelvir.