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.

Relationship of prepartum udder and teat measurements with subsequent milk production traits in primiparous Nili-Ravi buffaloes.

AIM: This study was conducted to find out the relationship of prepartum udder and teat measurements with subsequent milk production traits in primiparous Nili-Ravi buffaloes. MATERIALS AND METHODS: A total of 12 Nili-Ravi buffalo heifers were selected from Buffalo Farm, Central Institute for Research on Buffaloes, Regional Station- Bir Dosanjh, Nabha, Patiala, Punjab. The udder length (UL), udder width (UW), udder depth, teat length (TL), teat diameter (TD), and teat distances were measured at fortnightly interval from 60 days prepartum until calving. After calving, 60 days total milk yield (TDMY), peak yield (PY), and days taken to attain PY (DPY) were also recorded. The correlation coefficients of various prepartum udder and teat measurements since 60 days prepartum to calving with 60 days TDMY, PY, and DPY were calculated to find out the relationship between the traits in primiparous Nili-Ravi buffaloes. RESULTS: The result envisaged that all udder and teat measurements were increased gradually toward the date of calving in primiparous buffaloes. The UL, UW, left fore (LF) and right rear (RR)TL, RRTD, and the distance between LF to left rear (LR) teat were positively correlated with 60 days TDMY. The UL and UW depicted positive but nonsignificant correlation with PY. Fore TLs showed positive correlation where as TDs and teat distances had a negative correlation with the DPY in primiparous Nili-Ravi buffaloes. CONCLUSION: It was concluded that milk production performance could be assessed on the basis of prepartum udder and teat measurements in primiparous Nili-Ravi buffaloes.

Effect of management system and season on semen freezability in Jakhrana bucks.

AIM: The objective of the study was to determine the effect of the management system (intensive and semi-intensive) and season (autumn and winter) on semen freezability in Jakhrana bucks. MATERIALS AND METHODS: A total of 24 Jakhrana bucks of same body weight and age (BW=30 kg, age=1 year) were randomly allotted into two groups, viz., Group I (intensive system, 12 bucks) and Group II (semi-intensive system, 12 bucks). These two groups were statistically tested for their homogeneity with respect to age and BW. Semen was collected twice weekly using an artificial vagina during two seasons: autumn (September-November) and winter (December-February). A total of 240 semen samples (120 from each group and season) were evaluated for post-thaw motility (PTM), viability, abnormality, functional membrane integrity (hypo-osmotic swelling [HOS]) response and acrosomal integrity. RESULTS: The mean values of PTM and acrosomal integrity of spermatozoa were significantly (p<0.01) higher in Group II as compared to Group I. The mean values of viability and abnormality were also differed significant (p<0.05) between groups. However, the mean values of HOS response were found non-significant (p>0.05) between groups. The season showed a significant effect on all parameters except viability and HOS response. The PTM and acrosomal integrity of spermatozoa were significantly (p<0.01) higher in winter as compared to autumn season. Abnormality of spermatozoa was significantly (p<0.05) lower in winter season. CONCLUSIONS: This study indicates that both management system and season influence semen freezability. The semen collected from bucks reared under the semi-intensive system and winter season showed better semen freezability characteristics.

Effect of infrared lamps to ameliorate cold stress in Vrindavani calves.

AIM: This study was conducted to determine the effect of infrared lamps to ameliorate cold stress in Vrindavani (Holstein Friesian × Brown Swiss × Jersey × Hariana) calves. MATERIALS AND METHODS: For the present investigation, ten newborn Vrindavani calves were randomly divided into two groups (G1 and G2) of five each. The experiment was conducted from 2(nd) November to 8(th) February when the environmental temperature was at the lowest. The calves of G1 were provided with no additional protection while the calves of G2 were protected against the cold weather by providing heat using the infrared lamps. The body weight (kg) of the calves was recorded at weekly interval. The blood samples collected within 6 h of birth and then at fortnightly interval were analyzed for packed cell volume (PCV, %), hemoglobin (Hb, g/dl). Besides, the serum biochemical parameters, viz., Total serum protein (TSP, g/l), albumin (g/l), globulin (g/l), albumin globulin ratio (A:G) and important stress parameters, viz., triiodothyronine (T3, ng/ml), thyroxine (T4, ng/ml) and cortisol (ng/ml) were also estimated. RESULTS: The calves of G2 showed higher body weight gain as compared to G1. The differences were found to be highly significant (p<0.01). The calves in G1 showed comparatively higher values of PCV and Hb and the differences were found to be significant (p<0.05) on 45(th) day for PCV and highly significant (p<0.01) on 60(th) day for PCV and on 45(th) day for Hb. The values of TSP and albumin were comparatively higher in calves of G1 as compared to G2 and the differences were highly significant (p<0.01) on 45(th) day for both TSP and albumin and significant (p<0.05) on 60(th) day for albumin. Significantly (p<0.01) higher values of cortisol and T4 were observed on 15 and 45(th) day in calves of G1 as compared to G2. The T3 levels were also found higher in calves of G1 than G2 and the differences were significant (p<0.05) on 15 and 30(th) day and highly significant (p<0.01) on 45(th) day of the study. CONCLUSION: Based on the results, it could be concluded that the infrared lamps are efficient in providing favorable microclimate and hence can be effectively used in calf shed to protect newborn calves from adverse conditions of winter and to improve their body growth performance.

Relationship of udder and teat conformation with intra-mammary infection in crossbred cows under hot-humid climate.

AIM: The present study was aimed to investigate the relationship of udder shape, teat-end shape, teat length, and teat diameter with intra-mammary infection in Jersey crossbred cows under hot-humid climate. MATERIALS AND METHODS: A total of 24 lactating Jersey crossbred cows were evaluated for udder shape (pendulous/regular) and teat-end shape (flat/inverted/pointed) by visual examination, while teat length and teat diameter were measured using vernier caliper. Monthly milk sampling was done for 4 months of duration. Few quarters were found as blind or non-functional and so, a total of 366 quarter wise milk samples were collected at the monthly interval and subjected to somatic cell count (SCC) microscopically. The data on SCC were transformed into log scale and analyzed. RESULTS: There was a significant (p<0.01) effect of udder shape and teat-end shape on SCC level. The mean SCC level for pendulous udder was significantly (p<0.05) higher as compared to the regular shaped udder. Similarly, significantly (p<0.05) a higher level of mean SCC was found in flat teat-end shape. A significant (p<0.01) correlation was found between SCC and teat length as well as teat diameter. CONCLUSION: In conclusion, pendulous udder, flat and inverted teat-end, very long and thick teat were more susceptible to intra-mammary infection in Jersey crossbred cows and these traits must be considered accordingly while selecting dairy animals for future milk production.