SARS-CoV-2 journey: from alpha variant to omicron and its sub-variants.

The COVID-19 pandemic has affected hundreds of millions of individuals and caused more than six million deaths. The prolonged pandemic duration and the continual inter-individual transmissibility have contributed to the emergence of a wide variety of SARS-CoV-2 variants. Genomic surveillance and phylogenetic studies have shown that substantial mutations in crucial supersites of spike glycoprotein modulate the binding affinity of the evolved SARS-COV-2 lineages to ACE2 receptors and modify the binding of spike protein with neutralizing antibodies. The immunological spike mutations have been associated with differential transmissibility, infectivity, and therapeutic efficacy of the vaccines and the immunological therapies among the new variants. This review highlights the diverse genetic mutations assimilated in various SARS-CoV-2 variants. The implications of the acquired mutations related to viral transmission, infectivity, and COVID-19 severity are discussed. This review also addresses the effectiveness of human neutralizing antibodies induced by SARS-CoV-2 infection or immunization and the therapeutic antibodies against the ascended variants.

Current status in cellular-based therapies for prevention and treatment of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) outbreaks that resulted in a catastrophic threat to global health, with more than 500 million cases detected and 5.5 million deaths worldwide. Patients with a COVID-19 infection presented with clinical manifestations ranging from asymptomatic to severe symptoms, resulting in acute lung injury, acute respiratory distress syndrome, and even death. Immune dysregulation through delayed innate immune response or impairment of the adaptive immune response is the key contributor to the pathophysiology of COVID-19 and SARS-CoV-2-induced cytokine storm. Symptomatic and supportive therapy is the fundamental strategy in treating COVID-19 infection, including antivirals, steroid-based therapies, and cell-based immunotherapies. Various studies reported substantial effects of immune-based therapies for patients with COVID-19 to modulate the over-activated immune system while simultaneously refining the body's ability to destroy the virus. However, challenges may arise from the complexity of the disease through the genetic variance of the virus itself and patient heterogeneity, causing increased transmissibility and heightened immune system evasion that rapidly change the intervention and prevention measures for SARS-CoV-2. Cell-based therapy, utilizing stem cells, dendritic cells, natural killer cells, and T cells, among others, are being extensively explored as other potential immunological approaches for preventing and treating SARS-CoV-2-affected patients the similar process was effectively proven in SARS-CoV-1 and MERS-CoV infections. This review provides detailed insights into the innate and adaptive immune response-mediated cell-based immunotherapies in COVID-19 patients. The immune response linking towards engineered autologous or allogenic immune cells for either treatment or preventive therapies is subsequently highlighted in an individual study or in combination with several existing treatments. Up-to-date data on completed and ongoing clinical trials of cell-based agents for preventing or treating COVID-19 are also outlined to provide a guide that can help in treatment decisions and future trials.

Highly Diastereoselective Route to α-Glucosidase Inhibitors, Neosalacinol and Neoponkoranol.

A facile and highly diastereoselective route to potent natural α-glucosidase inhibitors, i.e., neosalacinol (4) and neoponkoranol (6), isolated from the traditional Ayurvedic medicine "Salacia" was developed by intramolecular cyclization of appropriately substituted sulfides (9 and 12).

Hydrophobic substituents increase the potency of salacinol, a potent α-glucosidase inhibitor from Ayurvedic traditional medicine 'Salacia'.

Using an in silico method, seven analogs bearing hydrophobic substituents (8a: Me, 8b: Et, 8c: n-Pent, 8d: n-Hept, 8e: n-Tridec, 8f: isoBu and 8g: neoPent) at the 3'-O-position in salacinol (1), a highly potent natural α-glucosidase inhibitor from Ayurvedic traditional medicine 'Salacia', were designed and synthesized. In order to verify the computational SAR assessments, their α-glucosidase inhibitory activities were evaluated in vitro. All analogs (8a-8g) exhibited an equal or considerably higher level of inhibitory activity against rat small intestinal α-glucosidases compared with the original sulfonate (1), and were as potent as or higher in potency than the clinically used anti-diabetics, voglibose, acarbose or miglitol. Their activities against human maltase exhibited good relationships to the results obtained with enzymes of rat origin. Among the designed compounds, the one with a 3'-O-neopentyl moiety (8g) was most potent, with an approximately ten fold increase in activity against human maltase compared to 1.

Role of the side chain stereochemistry in the α-glucosidase inhibitory activity of kotalanol, a potent natural α-glucosidase inhibitor.

Synthesis and evaluation of four diastereomers (9a, 9b, 9c and 9d) of kotalanol, a potent α-glucosidase inhibitor isolated from an Ayurvedic medicinal plant Salacia species, are described. Stereo-inversion at C-3' and C-4' of kotalanol (2) caused significant decrease of the inhibitory activities against maltase and sucrase, whereas inhibitory activity against isomaltase sustained, thus resulted in exerting selectivity against isomaltase.