ABSTRACT
COVID-19 caused a catastrophe in human health. People infected with COVID-19 also suffer from various clinical illnesses during and after the infection. The Boerhavia diffusa plant is well known for its antihypertensive activity. ACE-II inhibitors and calcium channel blockers are reported as mechanisms for the antihypertensive activity of B. diffusa phytoconstituents. Various studies have said ACE-II is the virus's binding site to attack host cells. COVID-19 treatment commonly employs a variety of synthetic antiviral and steroidal drugs. As a result, other clinical illnesses, such as hypertension and hyperglycemia, emerge as serious complications. Safe and effective drug delivery is a prime objective of the drug development process. COVID-19 is treated with various herbal treatments; however, they are not widely used due to their low potency. Many herbal plants and formulations are used to treat COVID-19 infection, in which B. diffusa is the most widely used plant. The current study relies on discovering active phytoconstituents with ACE-II inhibitory activity in the B. diffusa plant. As a result, it can be used as a treatment option for patients with COVID-19 and related diseases. Different phytoconstituents of the B. diffusa plant were selected from the reported literature. The activity of phytoconstituents against ACE-II proteins has been studied. Molecular docking and ligand-protein interaction computation tools are used in the In-silico experiment. Physicochemical, drug-likeness, water solubility, lipophilicity, and pharmacokinetic parameters are used to evaluate phytoconstituents. Liriodenine has the best drug-likeness, bioactivity, and binding score characteristics among the selected ligands. The In-silico study aims to find the therapeutic potential of B. diffusa phytoconstituents against ACE-II. Targeting ACE-II also shows an effect against SARS-CoV-2. It can serve as a rationale for designing a drug for patient infected with COVID-19and associated diseases.
ABSTRACT
In coronaviridae such as SARS-CoV-2, subgenomic RNAs (sgRNA) are replicative intermediates, therefore, their abundance and structures could infer viral replication activity and severity of host infection. Here, we systematically characterized the sgRNA expression and their structural variation in 81 clinical specimens collected from symptomatic and asymptomatic individuals with a goal of assessing viral genomic signatures of disease severity. We demonstrated the highly coordinated and consistent expression of sgRNAs from individuals with robust infections that results in symptoms, and found their expression is significantly repressed in the asymptomatic infections, indicating that the ratio of sgRNAs to genomic RNA (sgRNA/gRNA) is highly correlated with the severity of the disease. Using long read sequencing technologies to characterize full-length sgRNA structures, we also observed widespread deletions in viral RNAs, and identified unique sets of deletions preferentially found primarily in symptomatic individuals, with many likely to confer changes in SARS-CoV-2 virulence and host responses. Furthermore, based on the sgRNA structures, the frequently occurred structural variants in SARS-CoV-2 genomes serves as a mechanism to further induce SARS-CoV-2 proteome complexity. Taken together, our results show that differential sgRNA expression and structural mutational burden both appear to be correlated with the clinical severity of SARS-CoV-2 infection. Longitudinally monitoring sgRNA expression and structural diversity could further guide treatment responses, testing strategies, and vaccine development.
