In silico analysis of phytochemicals and non-phytochemicals and comparing their potentiality on inhibiting nsp12 and nsp14 in SARS-CoV-2 variants

ABSTRACT

The spread of SARS-CoV-2 and its variants, leads to global pandemic endangering human life and health. The primary challenge for the scientific community is to find a potential cure for the disease which can act on the emerging variants of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Due to the absence of effective medical treatment for the diseases, the healthcare system around the world was at a standstill. The nsp12 and nsp14 are one of the important proteins which are involved in the replication and proofreading of SARS-CoV-2 respectively. Both the non-structural proteins have highly conserved regions and served as a popular target for corona virus inhibitors for drug screening. In this study, the primary aim is to find the potential inhibitors, both phytochemical and nonphytochemical, which could act on variants to inhibit the activity of nsp12 and nsp14. Also to compare the binding affinity of nsp12 and nsp14 with phytochemicals and nonphytochemicals. A combination of mutational landscape, structure-based virtual screening and molecular dynamics (MD) simulation approaches were utilized in this work. From the mutational landscape, two functionally active mutations were observed in nsp12 and single mutation was observed in nsp14 of SARS CoV-2 Variants. The molecular simulation is performed for drugs Cepharanthine (phytochemical) and Hypericin (phytochemical) with top binding affinity for nsp12 variants and for molecules Hypericin (phytochemical) and conivaptan (non-Phytochemical) having top binding affinity with nsp14 wildtype and variants.