Structural evolution of Delta lineage of SARS-CoV-2.

One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein. Given that Spike is the main target of common treatments of COVID-19, mutations occurring at this virulent factor can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, being characterized by many Spike mutations inside and outside of its receptor-binding domain (RBD), shows high infectivity and relative resistance to existing cures. Here, utilizing a wide range of computational biology approaches, such as immunoinformatics, molecular dynamics (MD), analysis of intrinsically disordered regions (IDRs), protein-protein interaction analyses, residue scanning, and free energy calculations, we examine the structural and biological attributes of the B.1.617.2 Spike protein. Furthermore, the antibody design protocol of Rosetta was implemented for evaluation the stability and affinity improvement of the Bamlanivimab (LY-CoV55) antibody, which is not capable of interactions with the B.1.617.2 Spike. We observed that the detected mutations in the Spike of the B1.617.2 variant of concern can cause extensive structural changes compatible with the described variation in immunogenicity, secondary and tertiary structure, oligomerization potency, Furin cleavability, and drug targetability. Compared to the Spike of Wuhan lineage, the B.1.617.2 Spike is more stable and binds to the Angiotensin-converting enzyme 2 (ACE2) with higher affinity.

Investigation of the interactions of HSA and SARS-CoV-2 papain-like protease against eugenol for novel COVID-19 drug discovery: spectroscopic and insilico study.

Coronavirus family consist of a member known as SARS-CoV-2, spread drastically in 2019 (Covid-19), affecting millions of people worldwide. Till date there is no clear-clinical therapy or drug, targeted to cure this serious disease. Researches are going on to prevent this corona virus. Here, we tried to explore a novel SARS-CoV-2 papain-like protease as a potential inhibitor. Finally, eugenol was docked with this protease to find prime SARS-inhibitors. In silico studies revealed that eugenol binds to the active site of SARS-CoV-2 papain-like protease with appropriate binding. Moreover, the MD simulation for 100 ns and MMPBSA calculation reveals that eugenol possess potential phytotherapeutic properties against COVID-19. The interaction of eugenol with human serum albumin has been examined by using fluorescence, UV-vis spectroscopy, circular dichroism as well as computational techniques such as molecular docking, molecular dynamic simulation and MMPBSA calculation. Overall investigation shows eugenol having good affinity for HSA Ka 6.80 × 106 M-1.Communicated by Ramaswamy H. Sarma.

Structural Homology-Based Drug Repurposing Approach for Targeting NSP12 SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2, also known as SARS-CoV-2, is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 has a highly conserved non-structural protein 12 (NSP-12) involved in RNA-dependent RNA polymerase (RdRp) activity. For the identification of potential inhibitors for NSP-12, computational approaches such as the identification of homologous proteins that have been previously targeted by FDA-approved antivirals can be employed. Herein, homologous proteins of NSP-12 were retrieved from Protein DataBank (PDB) and the evolutionary conserved sequence and structure similarity of the active site of the RdRp domain of NSP-12 was characterized. The identified homologous structures of NSP-12 belonged to four viral families: Coronaviridae, Flaviviridae, Picornaviridae, and Caliciviridae, and shared evolutionary conserved relationships. The multiple sequences and structural alignment of homologous structures showed highly conserved amino acid residues that were located at the active site of the RdRp domain of NSP-12. The conserved active site of the RdRp domain of NSP-12 was evaluated for binding affinity with the FDA-approved antivirals, i.e., Sofosbuvir and Dasabuvir in a molecular docking study. The molecular docking of Sofosbuvir and Dasabuvir with the active site that contains conserved motifs (motif A-G) of the RdRp domain of NSP-12 revealed significant binding affinity. Furthermore, MD simulation also inferred the potency of Sofosbuvir and Dasabuvir. In conclusion, targeting the active site of the RdRp domain of NSP-12 with Dasabuvir and Sofosbuvir might reduce viral replication and pathogenicity and could be further studied for the treatment of SARS-CoV-2.

Ethnobotanical Study of Medicinal Plants Used against COVID-19.

During the COVID-19 pandemic, the Moroccan population, like the entire population of the world, used medicinal plants to treat or cure symptoms of SARS-CoV-2. The present work was designed to identify the medicinal plants used by the Moroccan population in the prevention or treatment of COVID-19. To achieve this goal, a survey was conducted to collect data on plants along with the sociodemographic parameters of users. The outcome of this work showed that 1,263 people were interviewed with 63.5% male, aged between 18 and 82 years. Most plant users were between 20 and 40 years, which constituted 80.1% of the study population. The level of education of participants was 70.9% university and 27.6% secondary. The most useful plants were eucalyptus, cloves, lemon, and garlic. Notably, 61.9% of interviewed people used plants for preventing or treating COVID-19: 30.6% of them declared one-time use from the beginning of the pandemic, and 47.8% declared frequent daily use until recovery, while 17.4% declared single daily use. Five out of twenty-one plants used in the treatment are known for their potential toxicity, including Artemisia herba-alba and oleander (Nerium oleander). The findings of the present work could serve society by providing potential medicinal plants to control COVID-19.