Repurposing of US-FDA approved drugs against SARS-CoV-2 main protease (Mpro) by using STD-NMR spectroscopy, in silico studies and antiviral assays.

SARS-CoV-2 Main protease (Mpro) is a well-known drug target against SARS-CoV-2 infection. Identification of Mpro inhibitors is vigorously pursued due to its crucial role in viral replication. The present study was aimed to identify Mpro inhibitors via repurposing of US-FDA approved drugs by STD-NMR spectroscopy. In this study, 156 drugs and natural compounds were evaluated against Mpro. Among them, 10 drugs were found to be interacting with Mpro, including diltiazem HCl (1), mefenamic acid (2), losartan potassium (3), mexiletine HCl (4), glaucine HBr (5), trimebutine maleate (6), flurbiprofen (7), amantadine HCl (8), dextromethorphan (9), and lobeline HCl (10) in STD-NMR spectroscopy. Their interactions were compared with three standards (Repurposed anti-viral drugs), dexamethasone, chloroquine phosphate, and remdesivir. Thermal stability of Mpro and dissociation constant (Kd) of six interacting drugs were also determined using DSF. RMSD plots in MD simulation studies showed the formation of stable protein-ligand complexes. They were further examined for their antiviral activity by plaque reduction assay against SARS-CoV-2, which showed 55-100% reduction in viral plaques. This study demonstrates the importance of drug repurposing against emerging and neglected diseases. This study also exhibits successful application of STD-NMR spectroscopy combined with plaque reduction assay in rapid identification of potential anti-viral agents.

Estimation of economic benefits associated with the reduction in the CO2 emission due to COVID-19

Since World War-II, the COVID-19 pandemic is considered the most serious challenge faced by the mankind. This pandemic has not only adversely affected the health systems but has also disrupted the manufacturing and industrial sectors and thus leading to low CO2 emissions. Reduction in the carbon dioxide (CO2) gas emission has been noticed nearly everywhere in the world due to shutdown of industries and lockdown imposed by governments as a consequence of the COVID-19 pandemic. In the year 2019, around 37 billion tons of CO2 emitted globally that has been reduced by 9% in the same period (January to July) for the year 2020 as consequence of COVID-19 pandemic. The Social Cost of Carbon (SCC) of a country reflects the economic damages caused by per ton increase in the CO2 emissions. Economic and environmental benefits are associated with the reduction of CO2 emissions as a result of COVID-19 and their estimation is the main theme of the study. Coupling reduction in the CO2 emissions to the Social Cost of Carbon gives economic benefit for a country. The research presented investigates the long term economic and environmental benefits associated with the reduction in the CO2 emissions for various regions of the world. The economic benefit due to the reduction in the of the CO2 emissions as consequence of the COVID-19 to global economy is estimated as 650 billion US Dollars for the period of 6 months (from January to July). The study mainly focuses on the countries that contribute the high percentage of CO2 emissions to the atmosphere. The first half of year 2020 (from January 2020 to July 2020) is taken into consideration because lockdown was mainly followed in that period. Further, within the country the sectors that contribute the high percentage of CO2 emissions are also taken into account.