A novel plant lectin, NTL-125, interferes with SARS-CoV-2 interaction with hACE2.

COVID-19 caused by SARS-CoV-2 virus has had profound impact on the world in the past two years. Intense research is going on to find effective drugs to combat the disease. Over the past year several vaccines were approved for immunization. But SARS-CoV-2 being an RNA virus is continuously mutating to generate new variants, some of which develop features of immune escape. This raised serious doubts over the long-term efficacy of the vaccines. We have identified a unique mannose binding plant lectin from Narcissus tazetta bulb, NTL-125, which effectively inhibits SARS-CoV-2 replication in Vero-E6 cell line. In silico docking studies revealed that NTL-125 has strong affinity to viral Spike RBD protein, preventing it from attaching to hACE2 receptor, the gateway to cellular entry. Binding analyses revealed that all the mutant variants of Spike protein also have stronger affinity for NTL-125 than hACE2. The unique α-helical tail of NTL-125 plays most important role in binding to RBD of Spike. NTL-125 also interacts effectively with some glycan moieties of S-protein in addition to amino acid residues adding to the binding strength. Thus, NTL-125 is a highly potential antiviral compound of natural origin against SARS-CoV-2 and may serve as an important therapeutic for management of COVID-19.

Identification of the binding interactions of some novel antiviral compounds against Nsp1 protein from SARS-CoV-2 (COVID-19) through high throughput screening.

The SARS-CoV-2 pandemic has become a global threat. It has become very difficult to control the spreading of the virus. The virus is a RNA virus and the virulence of the virus is mediated by three virulence causing proteins, viz., Nsp1, Nsp3c and ORF7. So far the drug designing endeavors against the virus have been being targeted towards the spike protein which is responsible for the entry of the virus inside human host as well as the RNA dependent RNA polymerase. However, no effective treatment against the virus has so far been developed. In the present situation, an attempt has been made to target the virulence protein factor Nsp1 which binds to the 40S ribosomal subunit of the human host. We tried to target the Nsp1 by in-silico virtual screening of ligand libraries. We built the three dimensional structure of Nsp1 and used the structure to screen the ChEMBL drug library. We used molecular docking simulations of the top6 screened ligands with Nsp1 and subjected the liagnd-Nsp1 complexes to molecular dynamics simulations to analyze the behaviors of the ligands in a virtual cell. From our analysis we could predict that the ligands bearing the ChEMBL identifiers, CHEMBL1096281, CHEMBL2022920, CHEMBL175656, had the best binding affinity values with Nsp1. Therefore, these ligand molecules may be tested in wet-lab for further analysis. This is the first report to target the virulence factor Nsp1 from SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

Repurposed drugs and nutraceuticals targeting envelope protein: A possible therapeutic strategy against COVID-19.

COVID-19 pandemic caused by SARS-CoV-2 has already claimed millions of lives worldwide due to the absence of a suitable anti-viral therapy. The CoV envelope (E) protein, which has not received much attention so far, is a 75 amino acid long integral membrane protein involved in assembly and release of the virus inside the host. Here we have used artificial intelligence (AI) and pattern recognition techniques for initial screening of FDA approved pharmaceuticals and nutraceuticals to target this E protein. Subsequently, molecular docking simulations have been performed between the ligands and target protein to screen a set of 9 ligand molecules. Finally, we have provided detailed insight into their mechanisms of action related to the varied symptoms of infected patients.