Ergoloid Mesylates

Malaysia reported the first human case of Nipah virus (NiV) in late September 1998 with encephalitis and respiratory symptoms. As a result of viral genomic mutations, two main strains (NiV-Malaysia and NiV-Bangladesh) have spread around the world. There are no licensed molecular therapeutics available for this biosafety level 4 pathogen. NiV attachment glycoprotein plays a critical role in viral transmission through its human receptors (Ephrin-B2 and Ephrin-B3), so identifying small molecules that can be repurposed to inhibit them is crucial to developing anti-NiV drugs. Consequently, in this study annealing simulations, pharmacophore modeling, molecular docking, and molecular dynamics were used to evaluate seven potential drugs (Pemirolast, Nitrofurantoin, Isoniazid Pyruvate, Eriodictyol, Cepharanthine, Ergoloid, and Hypericin) against NiV-G, Ephrin-B2, and Ephrin-B3 receptors. Based on the annealing analysis, Pemirolast for efnb2 protein and Isoniazid Pyruvate for efnb3 receptor were repurposed as the most promising small molecule candidates. Furthermore, Hypericin and Cepharanthine, with notable interaction values, are the top Glycoprotein inhibitors in Malaysia and Bangladesh strains, respectively. In addition, docking calculations revealed that their binding affinity scores are related to efnb2-pem (- 7.1 kcal/mol), efnb3-iso (- 5.8 kcal/mol), gm-hyp (- 9.6 kcal/mol), gb-ceph (- 9.2 kcal/mol). Finally, our computational research minimizes the time-consuming aspects and provides options for dealing with any new variants of Nipah virus that might emerge in the future.

Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV2) is responsible for fetal pneumonia called COVID19. SARS-CoV2 emerged in Wuhan, Hubei Province of China in December 2019. The COVID19 pandemic has now gripped the entire world with more than 70 million cases and over 1.5 million deaths so far. There no treatment option for COVID19 is in term of a drug or vaccine is currently available. Therefore drug repurposing may only provide a quick method for utilizing existing drugs for a therapeutic option. The virus genome contains several non-structural proteins (NSP) which serve as target for designing of antiviral agents. NSP9 of SARS-CoV2 encodes for a replicase enzyme which is essential for the virus replication in the host cell. In search of potent inhibitors, we have screened FDA approved drugs against NSP9 using in silico methods. Five drugs fluspirilene, troglitazone, alvesco, dihydroergotoxine and avodart were found to have highest affinities with the replicase. The molecular dynamics simulation (MDS) studies demonstrated strong drugs binding and stable NSP9-drugs complexes formation. The findings are also strongly supported by root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and hydrogen bond analysis of the complexes. Principal component analysis showed the stable conformation of NSP9 upon drug binding. It could be inferred that these five drugs individually or in combinations may be used as potential inhibitors of NSP9 of SARS-CoV-2 after exploring their in vivo antiviral potential.Communicated by Ramaswamy H. Sarma.