COVID-19: Diagnostics, Therapeutic Advances, and Vaccine Development.

PURPOSE OF REVIEW: Human race is currently facing the wrath of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly transmittable and pathogenic RNA virus, causing coronavirus disease 2019 (COVID-19), the worst ever global pandemic. Coronaviruses (CoVs) have emerged as a major public health concern. Urgent global response to COVID-19 outbreak has been to limit spread of SARS-CoV-2 via extensive monitoring and containment. Various treatment regimens have been adopted to manage COVID-19, with known drugs and drug combinations used to decrease the morbidity and mortality associated with COVID-19. Intensive research on various fronts including studying molecular and structural aspects of these viruses and unraveling the pathophysiology and mechanistic basis of COVID-19 aimed at developing effective prophylactic, therapeutic agents and vaccines has been carried out globally. RECENT FINDINGS: No approved antiviral treatment except remdesivir exists for SARS-CoV-2 till date though novel drug targets have been identified. However, worldwide frantic and competitive vaccine development pharmaceutical race has borne fruit in the form of a number of promising candidate vaccines, out of which few have already received emergency use authorization by regulatory bodies in record time. SUMMARY: This review highlights the painstaking efforts of healthcare workers and scientific community to successfully address the COVID-19 pandemic-though damage in the form of severe illness, loss of lives, and livelihood has left a serious mark. Focusing on extensive research on various therapeutic options and antiviral strategies including neutralizing antibodies, potential drugs, and drug targets, light has been shed on various diagnostic options and the amazing vaccine development process as well.

Managing the COVID-19 Pandemic: Research Strategies Based on the Evolutionary and Molecular Characteristics of Coronaviruses.

Coronavirus disease 2019 (COVID-19), an ongoing global health emergency, is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging in Wuhan, China, in December 2019, it spread widely across the world causing panic-worst ever economic depression is visibly predictable. Coronaviruses (CoVs) have emerged as a major public health concern having caused three zoonotic outbreaks; severe acute respiratory syndrome-CoV (SARS-CoV) in 2002-2003, Middle East respiratory syndrome-CoV (MERS-CoV) in 2012, and currently this devastating COVID-19. Research strategies focused on understanding the evolutionary origin, transmission, and molecular basis of SARS-CoV-2 and its pathogenesis need to be urgently formulated to manage the current and possible future coronaviral outbreaks. Current response to the COVID-19 outbreak has been largely limited to monitoring/containment. Although frantic global efforts for developing safe and effective prophylactic and therapeutic agents are on, no licensed antiviral treatment or vaccine exists till date. In this review, research strategies for coping with COVID-19 based on evolutionary and molecular aspects of coronaviruses have been proposed.

Impact of catechol-O-methyltransferase gene variants on methylation status of P16 and MGMT genes and their downregulation in colorectal cancer.

Globally, colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second most commonly diagnosed cancer in females, with 1.4 million new cases and almost 694 000 deaths estimated to have occurred in 2012. The development and progression of CRC is dictated by a series of alterations in diverse genes mostly proto-oncogenes and tumor suppressor genes. In this dreadful disease disturbances different from mutations called as epigenetic regulations are also taken into consideration and are thoroughly investigated. The present study was designed to analyze the promoter hypermethylation of CpG (cytosine, followed by guanine nucleotide) islands of cyclin-dependent kinase inhibitor 2A (P16) and O-methylguanine-DNA methyltransferase (MGMT) genes and its subsequent effect on the protein expression in CRC. The impact of the common functional polymorphism of the catechol-O-methyltransferase (COMT) gene, Val158Met, on promoter hypermethylation of P16 and MGMT genes in CRC was also investigated. The study included 200 CRC cases and equal numbers of normal samples. DNA was extracted using the kit method and methylation specific-PCR was performed for analysis of the promoter hypermethylation status. Total protein was isolated form all CRC cases and western blotting was performed for P16 and MGMT proteins. The COMT Val158Met polymorphism was analyzed by a PCR-restriction fragment length polymorphism assay. Epigenetic analysis showed that unlike other high-risk regions, the Kashmiri population has a different promoter hypermethylation profile of both P16 and MGMT genes, with frequent and significant promoter hypermethylation of both in CRC. The frequency of promoter hypermethylation of both genes was significantly higher in males and was insignificantly found to be higher in stage III/IV. The degree of P16 and MGMT promoter hypermethylation increased significantly with increasing severity of the lesion. We also found a significant correlation between P16 and MGMT promoter hypermethylation and loss of protein expression in CRC. A significant association was found between COMT polymorphism (homozygous variant) and P16 methylation status. Similar results were also found for MGMT hypermethylated cases.

Polymorphism of the XRCC3 gene and risk of gastric cancer in a Kashmiri population: a case-control study.

DNA repair plays a critical role in protecting the genome of the cell from the insults of cancer-causing agents. Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with the risk of developing cancer. Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity and genetic susceptibility to different cancers. The X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) gene is a member of the RAD51 gene family. It encodes an important protein that functions in the homologous recombination repair of a DNA double-strand break. For gastric cancer, the importance of mutations in mismatch repair genes has been well documented, but less is known about other DNA repair pathways in gastric carcinogenesis. In this study, we have focused on the XRCC3 gene, involved in homologous recombinational repair. The Kashmir valley has an increased incidence of gastric cancer and its etiology has not been understood fully as yet. As the Kashmiri population is ethnically and demographically different from that in other parts of the world, the aim of this study was to determine whether a single nucleotide polymorphism of the XRCC3 gene (Thr241Met) of exon 7 can influence the risk of gastric cancer in the population. As many as 80 histopathologically confirmed gastric cancer cases and 70 healthy controls, age, sex, and ethnicity matched for known genotypes of XRCC3 exon 7 were studied. We genotyped for this variant using PCR-restriction fragment length polymorphisms. The XRCC3 genotype and allele frequencies were not significantly different between cases and controls (P=0.92 for the genotype; P=0.72 for the allele). The XRCC3 241Met allele frequency (6.6%) was significantly lower in healthy Kashmiri controls than reported previously in healthy US White controls (38.9%). Compared with the XRCC3 241Thr/Thr genotype, the variant XRCC3 241Thr/Met and Met/Met genotypes were not associated with an increased risk of gastric cancer (adjusted odds ratio=1.19; 95% confidence interval=0.44-3.18). These findings suggest that polymorphisms of XRCC3 Thr241Met may not play a role in the etiology of gastric cancer. Further studies with a larger number of participants and simultaneous measurement of different polymorphisms in DNA repair genes in the same pathway are needed.