Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection.

Background: SARS-CoV-2 infection or COVID-19 is a major global public health issue that requires urgent attention in terms of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19. Purpose: The study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID-19. Methods: Homology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool. Results: Three compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin. Conclusion: This study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19.

Increase in SARS-CoV-2 infected biomedical waste among low middle-income countries: environmental sustainability and impact with health implications.

Studies have shown that severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) is a highly infectious disease, with global deaths rising to about 360,438 as of 28 May 2020. Different countries have used various approaches such as lockdown, social distancing, maintenance of personal hygiene, and increased establishment of testing and isolation centers to manage the pandemic. Poor biomedical waste (BMW) management, treatment, and disposal techniques, especially SARS-CoV-2 infected BMW, may threaten the environmental and public health in most developing countries and, by extension, impact the economic status of individuals and the nation at large. This may increase the potential for the transmission of air/blood body fluid-borne pathogens, increase the growth of microorganisms, risk of mutagenesis, and upsurge of more virulent strain. In contrast, uncontrolled substandard burning could increase the potential spread of nosocomial infection and environmental exposure to toxic organic compounds, heavy metals, radioactive, and genotoxic bio-aerosols which might be present in the gaseous, liquid, and solid by-products. The paucity of understanding of pathophysiology and management of the SARS-CoV-2 pandemic has also necessitated the need to put in place appropriate disposal techniques to cater for the sudden increase in the global demand for personal protective equipment (PPE) and pharmaceutical drugs to manage the pandemic and to reduce the risk of preventable infection by the waste. Therefore, there is a need for adequate sensitization, awareness, and environmental monitoring of the impacts of improper handling of SARS-CoV-2 infected BMWs. Hence, this review aimed to address the issues relating to the improper management of increased SARS-CoV-2 infected BMW in low middle-income countries (LMICs).

Testis and blood-testis barrier in Covid-19 infestation: role of angiotensin-converting enzyme 2 in male infertility.

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes COVID-19 infections penetrates body cells by binding to angiotensin-converting enzyme-2 (ACE2) receptors. Evidence shows that SARS-CoV-2 can also affect the urogenital tract. Hence, it should be given serious attention when treating COVID-19-infected male patients of reproductive age group. Other viruses like HIV, mumps, papilloma and Epstein-Barr can induce viral orchitis, germ cell apoptosis, inflammation and germ cell destruction with attending infertility and tumors. The blood-testis barrier (BTB) and blood-epididymis barrier (BEB) are essential physical barricades in the male reproductive tract located between the blood vessel and seminiferous tubules in the testes. Despite the significant role of these barriers in male reproductive function, studies have shown that a wide range of viruses can still penetrate the barriers and induce testicular dysfunctions. Therefore, this mini-review highlights the role of ACE2 receptors in promoting SARS-CoV-2-induced blood-testis/epididymal barrier infiltration and testicular dysfunction.