Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergence has resulted in a global health crisis. As a consequence, discovering an effective therapy that saves lives and slows the spread of the pandemic is a global concern currently.
In silico
drug repurposing is highly regarded as a precise computational method for obtaining fast and reliable results. Transmembrane serine-type 2 (TMPRSS2) is a SARS CoV-2 enzyme that is essential for viral fusion with the host cell. Inhibition of TMPRSS2 may block or lessen the severity of SARS-CoV-2 infection. In this study, we aimed to perform an
in silico
drug repurposing to identify drugs that can effectively inhibit SARS-CoV-2 TMPRSS2. As there is no 3D structure of TMPRSS2 available, homology modeling was performed to build the 3D structure of human TMPRSS2. 3848 world-approved drugs were screened against the target. Based on docking scores and visual outcomes, the best-fit drugs were chosen. Molecular dynamics (MD) and density functional theory (DFT) studies were also conducted. Five potential drugs (Amikacin, isepamicin, butikacin, lividomycin, paromomycin) exhibited promising binding affinities. In conclusion, these findings empower purposing these agents.
Over the last decades, genetics has been the engine that has pushed us along on our voyage to understand the etiology of Parkinson’s disease (PD). Although a large number of risk loci and causative mutations for PD have been identified, it is clear that much more needs to be done to solve the missing heritability mystery. Despite remarkable efforts, as a field, we have failed in terms of diversity and inclusivity. The vast majority of genetic studies in PD have focused on individuals of European ancestry, leading to a gap of knowledge on the existing genetic differences across populations and PD as a whole. As we move forward, shedding light on the genetic architecture contributing to PD in non-European populations is essential, and will provide novel insight into the generalized genetic map of the disease. In this review, we discuss how better representation of understudied ancestral groups in PD genetics research requires addressing and resolving all the challenges that hinder the inclusion of these populations. We further provide an overview of PD genetics in the clinics, covering the current challenges and limitations of genetic testing and counseling. Finally, we describe the impact of worldwide collaborative initiatives in the field, shaping the future of the new era of PD genetics as we advance in our understanding of the genetic architecture of PD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.