ABSTRACT
SARS-CoV-2, an etiological agent of COVID-19, has been the reason for the unexpected global pandemic, causing severe mortality and imposing devastative effects on public health. Despite extensive research work put forward by scientist around globe, so far, no suitable drug or vaccine (safe, affordable, and efficacious) has been identified to treat SARS-CoV-2. As an alternative way of improvising the COVID-19 treatment strategy, that is, strengthening of host immune system, a great deal of attention has been given to phytocompounds from medicinal herbs worldwide. In a similar fashion, the present study deliberately focuses on the phytochemicals of three Indian herbal medicinal plants viz., Mentha arvensis, Coriandrum sativum, and Ocimum sanctum for their efficacy to target well-recognized viral receptor protein through molecular docking and dynamic analyses. Nucleocapsid phosphoprotein (N) of SARS-CoV-2, being a pivotal player in replication, transcription, and viral genome assembly, has been recognized as one of the most attractive viral receptor protein targets for controlling the viral multiplication in the host. Out of 127 phytochemicals screened, nine (linarin, eudesmol, cadinene, geranyl acetate, alpha-thujene, germacrene A, kaempferol-3-O-glucuronide, kaempferide, and baicalin) were found to be phenomenal in terms of exhibiting high binding affinity toward the catalytic pocket of target N-protein. Further, the ADMET prediction analysis unveiled the non-tumorigenic, noncarcinogenic, nontoxic, non-mutagenic, and nonreproductive nature of the identified bioactive molecules. Furthermore, the data of molecular dynamic simulation validated the conformational and dynamic stability of the docked complexes. Concomitantly, the data of the present study validated the anti-COVID efficacy of the bioactives from selected medicinal plants of Indian origin.
ABSTRACT
BACKGROUND: COVID-19, the presently prevailing global public health emergency has culminated in international instability in economy. This unprecedented pandemic outbreak pressingly necessitated the trans-disciplinary approach in developing novel/new anti-COVID-19 drugs especially, small molecule inhibitors targeting the seminal proteins of viral etiological agent, SARS-CoV-2. METHODS: Based on the traditional medicinal knowledge, we made an attempt through molecular docking analysis to explore the phytochemical constituents of three most commonly used Indian herbs in 'steam inhalation therapy' against well recognized viral receptor proteins. RESULTS: A total of 57 phytochemicals were scrutinized virtually against four structural protein targets of SARS-CoV-2 viz. 3CLpro, ACE-2, spike glycoprotein and RdRp. Providentially, two bioactives from each of the three plants i.e. apigenin-o-7-glucuronide and ellagic acid from Eucalyptus globulus; eudesmol and viridiflorene from Vitex negundo and; vasicolinone and anisotine from Justicia adhatoda were identified to be the best hit lead molecules based on interaction energies, conventional hydrogen bonding numbers and other non-covalent interactions. On comparison with the known SARS-CoV-2 protease inhibitor -lopinavir and RdRp inhibitor -remdesivir, apigenin-o-7-glucuronide was found to be a phenomenal inhibitor of both protease and polymerase, as it strongly interacts with their active sites and exhibited remarkably high binding affinity. Furthermore, in silico drug-likeness and ADMET prediction analyses clearly evidenced the usability of the identified bioactives to develop as drug against COVID-19. CONCLUSION: Overall, the data of the present study exemplifies that the phytochemicals from selected traditional herbs having significance in steam inhalation therapy would be promising in combating COVID-19.