SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural–function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring “flu-like shots” annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.

Objectives Detection of hepatitis B surface antigen (HBsAg) plays an important role in the screening and diagnosis of hepatitis B virus (HBV) infections. There is a need of highly sensitive assays with an improved lower limit of detection (LoD). Here, we evaluate the performance characteristics of the HBsAg NEXT (HBsAg new) assay in the detection of HBsAg in clinical samples. Materials and Methods This was a cross-sectional study conducted at a tertiary care liver center in North India. The study included 439 clinical samples. The HBsAg new assay was compared to the conventional chemiluminescence-based assay (HBsAg old assay, Architect, Abbott Diagnostics, United States). The analytical sensitivity of the HBsAg new assay was evaluated by checking its performance with the second World Health Organization (WHO) international standards for HBsAg. Results Out of 439 blood samples that were retrieved from the departmental repository stored at –80°C, 100 samples were positive and 339 samples were negative for HBsAg as per the HBsAg old assay. The HBsAg new assay showed incremental detection of HBsAg in 11 additional samples. Out of these, 5 samples were confirmed as occult HBV infection and the remaining 6 were classified as “exposed-to-virus” samples (HBV core total antibody-positive). The HBsAg new assay demonstrated a high positive significant correlation with the HBsAg old assay (r = 0.881, p-value < 0.001). The HBsAg new assay could effectively detect the second WHO international standards to the level of 0.0033 IU/mL. Conclusion The HBsAg NEXT assay is a highly sensitive assay with an improved lower LoD.

Hepatitis C Virus (HCV) genotype (GT) 6 demonstrates maximum genomic diversity out of all the known genotypes of HCV, attributable to its inherent intra-genotype and inter-genotype recombination property. This is the most common genotype seen in HCV/HIV co-infected cases. HIV/HCV co-infection is linked with increased genetic diversity in HCV structural genes. The detailed information on the distribution of HCV GT6, its subtypes, and resistance to currently available antiviral drugs is limited in the Indian subcontinent. Therefore, in this single-center retrospective cross-sectional study, we aimed to map the occurrence of HCV GT6, its subtypes and resistance-associated substitution (RAS), and its correlation with antiviral treatment response in HCV-infected patients. From a cohort of 2052 HCV-infected patients, the overall prevalence of GT6 was 2.5% (n = 53), with a maximum of 81.1% (n = 43) seen in HCV/HIV co-infected patients. Nine different subtypes, 6a, 6b, 6f, 6i, 6n, 6u, 6v, 6w, and 6xa, were detected in the Indian population for the first time, with a predominance of 6xa (41.5%), a rare subtype, followed by 6n (39.6%). The phylogenetic analysis by the neighbor-joining method revealed three prominent viral clades, 6v, 6n, and 6xa–6u. The baseline (before treatment initiation) plasma samples of all GT6-infected patients were retrieved from −80 °C and a part of the NS5a and NS5b region of the viral genome was analyzed for the presence of RAS. No RASs were seen in the NS5b region, while in two patients (3.7%) RASs were seen at baseline in the NS5a region of the virus. Sustained viral response (SVR) was attained in 81% (n = 43) of patients. No difference in GT6 subtype distribution or occurrence of RAS was seen between mono-infected HCV and HIV/HCV co-infected cases. Our study revealed that RAS at baseline did not influence the attainment of SVR and the currently available antiviral therapy is effective against GT6 mono-infected and HIV/HCV co-infected patients.

Rapid detection of viruses is necessary for early diagnosis of the disease and initiation of treatment. However, currently popular quantitative polymerase chain reaction (qPCR) techniques involve multistep protocols which consume a lot of time and also use expensive optics for yielding accurate results. Electrochemical biosensors have developed into reliable analytical tools over the past decade for sensitive, specific and rapid detection of many viruses. Electrochemical impedance spectroscopy (EIS) is being used more frequently in electrochemical sensors and biosensors for both characterizing the sensors throughout the various phases of sensor design, as well as a method for quantitative and qualitative measurements. In this study, a sensitive electronic detection scheme for viral RNA is developed based on non-faradaic EIS. Impedance measurements corresponding to biomodification on the electrode surface is carried out through an in-house micro-chip. Sensitivity is included through gold nanoparticle labeling to the DNA primers and a dielectrophoretic (DEP) concentration step. All the tests are conducted with cDNA synthesized from Hepatitis C virus (HCV) RNA samples and the Limit of detection (LOD) achieved through the currently developed chip is in the range of 30 to 35 ng/μL i.e., around 140 nM for a 327 bp cDNA molecule. Further, the device starts detection procedure within 15 minutes of initiation.

Hepatitis C virus (HCV) is a bloodborne pathogen that can cause chronic liver disease and hepatocellular carcinoma. The loss of CpGs from virus genomes allows escape from restriction by the host zinc-finger antiviral protein (ZAP). The evolution of HCV in the human host has not been explored in the context of CpG depletion. We analysed 2616 full-length HCV genomes from 1977 to 2021. During the four decades of evolution in humans, we found that HCV genomes have become significantly depleted in (a) CpG numbers, (b) CpG O/E ratios (i.e., relative abundance of CpGs), and (c) the number of ZAP-binding motifs. Interestingly, our data suggests that the loss of CpGs in HCV genomes over time is primarily driven by the loss of ZAP-binding motifs; thus suggesting a yet unknown role for ZAP-mediated selection pressures in HCV evolution. The HCV core gene is significantly enriched for the number of CpGs and ZAP-binding motifs. In contrast to the rest of the HCV genome, the loss of CpGs from the core gene does not appear to be driven by ZAP-mediated selection. This work highlights CpG depletion in HCV genomes during their evolution in humans and the role of ZAP-mediated selection in HCV evolution.