ABSTRACT
The SARS-CoV-2 has infected many people globally with the ravaging COVID-19; a disease, which has become challenging for every aspect of modern healthcare. The saliva and oral mucosa are sites of high risk for increased viral loads, and aside from the usual epithelial functions like lining and protection, the oral mucosa is also specialized for crucial functions, such as secretion, mastication, sensory perception, and taste perception. The human ACE2 receptor has been extensively studied for its essential role in the regulation of blood pressure homeostasis. However, scRNA-Seq studies have revealed high expression levels of the protein in keratinized epithelial surfaces of the oral cavity. The SARS-CoV-2 have access to the host's body by binding to the ACE2 receptor, leading to the cleavage and major conformational changes in the viral spike glycoprotein for the release of its nucleocapsid into the cellular cytoplasm. This proteolytic cleavage is carried out by the TMPRSS2 and cathepsin L. In this study, we harnessed the information from the binding interface of TMPRSS2 and PAI-1 (a protease inhibitor known to inhibit the TMPRSS2 and several other proteases) to design a potential therapeutic peptide for the inhibition of the TMPRSS2, while also emphasizing the need for preventive masking. Supplementary Information: The online version contains supplementary material available at 10.1186/s43042-022-00213-z.
ABSTRACT
Background: The 2019-nCoV which is regarded as a novel coronavirus is a positive-sense single-stranded RNA virus. It is infectious to humans and is the cause of the ongoing coronavirus outbreak which has elicited an emergency in public health and a call for immediate international concern has been linked to it. The coronavirus main proteinase which is also known as the 3C-like protease (3CLpro) is a very important protein in all coronaviruses for the role it plays in the replication of the virus and the proteolytic processing of the viral polyproteins. The resultant cytotoxic effect which is a product of consistent viral replication and proteolytic processing of polyproteins can be greatly reduced through the inhibition of the viral main proteinase activities. This makes the 3C-like protease of the coronavirus a potential and promising target for therapeutic agents against the viral infection. Results: This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Comparative physiochemical studies were carried out on the resultant target protein and its template while selected HIV protease inhibitors were docked against the protein binding sites which contained no co-crystallized ligand. Conclusion: In line with results from this study which has shown great consistency with other scientific findings on coronaviruses, we recommend the administration of the selected HIV protease inhibitors as first-line therapeutic agents for the treatment of the current coronavirus epidemic.
ABSTRACT
The reversible process where a homogenous fluid de-mixes into two distinctively separate liquid phases is referred to as LLPS (Liquid-liquid phase separation). The resulting liquid is made up of one dilute phase and one condensed phase. An increasing number of studies have shown that the liquid-liquid phase separation is an important principle that underlies intracellular organization in biological systems, forming liquid condensates without a membrane envelope, otherwise known as MLOs (membraneless organelles). Such organelles include the P bodies, nucleolus and stress granules. Moreover, the regulation of many other biological processes such as signal transduction, chromatin rearrangement and RNA metabolism have been linked to the liquid-liquid phase separation.
