In silico, In vitro Screening of Plant Extracts for Anti-SARS-CoV-2 Activity and Evaluation of Their Acute and Sub-Acute Toxicity

Damle, Latha; Damle, Hrishikesh; Ganju, Shiban; Chandrashekar, C; Bharath, BR

Background In the absence of a specific drug for COVID 19, treatment with plant extracts could be an option worthy of further investigation. Purpose To screen the phytochemicals for Anti-SARS-CoV-2 in silico and evaluate their safety and efficacy in vitro and in vivo. Method The phytochemicals for Anti-SARS-CoV-2 were screened in silico using molecular docking. The hits generated from in silico screening were subjected for extraction, isolation and purification. The anti-SARS-CoV-2 activity of plant extracts of Z. piperitum (ATRI-CoV-E1), W. somnifera (ATRI-CoV-E2), C. inophyllum (ATRI-CoV-E3), A. paniculata (ATRI-CoV-E4), and C. Asiatica (ATRI-CoV-E5). The in vitro safety and anti-SARS-CoV-2 activity of plant extracts were performed in VeroE6 cells using Remdesivir as positive control. The acute and sub-acute toxicity study was performed in Wistar male and female rats. Results The percentage of cell viability for ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 treated VeroE6 cells were remarkably good on the 24th and 48th hour of treatment. The in vitro anti-SARS-CoV-2 activity of ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 were significant for both E gene and N gene. The percentage of SARS-CoV-2 inhibition for ATRI-COV-E4 was better than Remdesivir. For E gene and N gene, Remdesivir showed IC50 of 0.15 µM and 0.11 µM respectively, For E gene and N gene, ATRI-CoV-E4 showed IC50 of 1.18 µg and 1.16 µg respectively. Taking the clue from in vitro findings, the plant extracts A. paniculata (ATRI-COV-E4), W. somnifera extract (ATRI-COV-E5) and C. asiatica extract (ATRI-COV-E2) were combined (ATRICOV 452) and evaluated for acute and sub-acute toxicity in Wistar male and female rats. No statistically significant difference in haematological, biochemical and histopathological parameters were noticed. Conclusion The study demonstrated the Anti-SARS-CoV-2 activity in vitro and safety of plant extracts in both in vitro and in vivo experimental conditions.