ABSTRACT
In viral binding and entry, the Spike(S) protein of SARS-CoV-2 uses transmembrane serine protease 2 (TMPRSS2) for priming to cleavage themselves. In this study, we have screened 'drug-like' 7476 ligands and found that over thirty ligands can effectively inhibit the TMPRSS-2 better than the control ligand. Finally, the three best drug agents L1, L2, and L6 were selected according to their average binding affinities and fitting score. These ligands interact with Asp435, Cys437, Ser436, Trp461, and Cys465 amino acid residues. The three best candidates and a reported drug Nafamostat mesylate (NAM) were selected to run 250 ns molecular dynamics (MD) simulations. Various properties of ligand-protein interactions obtained from MD simulation such as bonds, angle, dihedral, planarity, coulomb, and van der Waals (VdW) were used for principal component analysis (PCA) calculation. PCA discloses the evidence of the structural similarities to the corresponding complexes of L1, L2, and L6 with the complex of TMPRSS2(TM) and Nafamostat mesylate (TM-NAM). Moreover, Quantitative structure-activity relationship (QSAR) pattern recognition was generated using PCA for the investigation of structural similarities among the selected ligands. Multiple Linear Regression (MLR) model was built to predict the binding energy compared to the binding energy obtained from molecular docking. The MLR regression model reveals an accuracy of 80% for the prediction of the binding energy of ligands. ADMET analysis demonstrates that these drug agents are appeared to be safer inhibitors. These three ligands can be used as potential inhibitors against the TMPRSS2.Communicated by Ramaswamy H. Sarma.
ABSTRACT
BACKGROUND: The outbreak of coronavirus infectious disease-2019 (COVID-19) is globally deemed a significant threat to human life. Researchers are searching for prevention strategies, mitigation interventions, and potential therapeutics that may reduce the infection's severity. One such means that is highly being talked in online and in social media is vitamin C. MAIN TEXT: Vitamin C is a robust antioxidant that boosts the immune system of the human body. It helps in normal neutrophil function, scavenging of oxidative species, regeneration of vitamin E, modulation of signaling pathways, activation of pro-inflammatory transcription factors, activation of the signaling cascade, regulation of inflammatory mediators, and phagocytosis and increases neutrophil motility to the site of infection. All of these immunological functions are required for the prevention of COVID-19 infection. CONCLUSION: Considering the role of vitamin C, it would be imperative to administrate vitamin C for the management of severe COVID-19. However, there is no specific clinical data available to confirm the use of vitamin C in the current pandemic.
ABSTRACT
BACKGROUND: COVID-19, a respiratory tract infection caused by SARS-CoV-2, is a burning question worldwide as it gives rise to a pandemic situation. No specific medications are still recommended for COVID-19; however, healthcare support is crucial for ameliorating the disease condition. Pharmacists are the frontline fighters who are responsible for providing healthcare support to the COVID-19 infected patients around the world. This review endeavored to briefly rationalize the contributions of several pharmacy professionals in diverse fields along with their collaborative efforts and dedication regarding their limitations during the COVID-19 situation and view the prospects of pharmaceutical care services in the post-pandemic period. MAIN BODY OF THE ABSTRACT: Online databases were utilized to search for scholarly articles and organizational websites, to sum up the information about the contemporary and expanded role of pharmacists. Key articles were retrieved from Google Scholar, PubMed, and Science Direct databases using terms: "COVID-19," "novel coronavirus," "community," "industrial," "hospital," "clinical," "recognition," "obstacles," "collaboration," "SARS-CoV-2," "healthcare," and "outbreak" in combination with "pharmacist." The articles were included from the inception of the pandemic to January 25, 2021. The current review found pharmacist's global contributions and involvements with other professionals to provide healthcare services amidst COVID-19. This included testing of suspects, providing medical information, psycho-social support, debunking myths, mitigating drug shortage events, telemedicine, e-prescription, infection control, and controlling the drug supply chain. In many countries, pharmacists' activities were much appreciated but in some countries, they were not properly acknowledged for their contributions amidst COVID-19 outbreak. They played additional roles such as participating in the antimicrobial stewardship team, improving value-added services, conducting clinical data analysis to suppress the outspread of the SARS-CoV-2. SHORT CONCLUSION: During the COVID-19 pandemic while the whole world is fighting against an invisible virus, the pharmacists are the earnest hero to serve their responsibilities along with additional activities. They need to be prepared and collaborate with other healthcare professionals further to meet the challenges of post-pandemic circumstances.
ABSTRACT
The new coronavirus (CoV), called novel coronavirus disease 2019 (COVID-19), belongs to the Coronaviridae family which was originated from the sea market in Wuhan city in China, at the end of the year 2019. COVID-19 and severe acute respiratory syndrome (SARS) are belonging to the same family (Coronaviridae). The current outbreak of COVID-19 creates public concern and threats all over the world and now it spreads out to more than 250 countries and territories. The researchers and scientists from all over the world are trying to find out the therapeutic strategies to abate the morbidity and mortality rate of the COVID-19 pandemic. The replication, spreading, and severity of SARS-CoV2 depend on environmental settings. Noteworthy, meteorological parameters are considered as crucial factors that affect respiratory infectious disorders, although the controversial effect of the meteorological parameter is exposed against COVID-19. Besides, COVID-19 accelerates the pathogenesis of the neurological disorders. However, the pathogenic mechanisms between COVID-19 and neurological disorders are still unclear. Hence, this review is focused on the genomics and ecology of SARS-CoV2 and elucidated the effects of climatic factors on the progression of COVID-19. This review also critically finds out the vulnerability between COVID-19 and neurological disorders based on the latest research data.