Co-infection of respiratory pathogens in SARS-CoV-2 positive patients at North West India, Rajasthan.

PURPOSE: Infection due to SARS-CoV-2 shows wide spectrum of disease from asymptomatic to severe disease and death. Coinfection of SARS-CoV-2 with other respiratory pathogens may affect the severity of disease and its outcome. Identification of other respiratory pathogens may help to initiate proper management and avoid unnecessary complications. MATERIALS AND METHODS: Total 250 SARS-COV-2 positive patients admitted in S.M.S hospitalwere included in study. Throat and nasopharyngeal swabs samples were collected in Viral Transport Medium (VTM) and nucleic acid extraction was done by automated EasyMag extractor and tested for 20 respiratory viruses and two bacteria by real time PCR. RESULTS: Out of 250 SARS CoV2 positive samples, 176 (70%) were positive for other respiratory pathogens also. The highest co-infection was due to HCoVOC43 (32.8%) virus followed by bacterial co-infection with S. pneumoniae (14.8%). Six (2.4%) patients with co-infection were on ventilator with age >65yr and three (1.2%) died during treatment. All three cases were found to have other co-morbid diseases like; asthma, Parkinson's and hypertension. CONCLUSION: High number of patients were found to have coinfection with other viruses and bacteria, timely identification and providing specific treatment to these patients can help improve outcome.

Genomic profile of SARS-CoV-2 Omicron variant and its correlation with disease severity in Rajasthan.

Background: Omicron, a new variant of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), was first detected in November 2021. This was believed to be highly transmissible and was reported to evade immunity. As a result, an urgent need was felt to screen all positive samples so as to rapidly identify Omicron cases and isolate them to prevent the spread of infection. Genomic surveillance of SARS-CoV-2 was planned to correlate disease severity with the genomic profile. Methods: All the SARS-CoV-2 positive cases detected in the state of Rajasthan were sent to our Lab. Samples received from 24 November 2021 to 4 January 2022 were selected for Next-Generation Sequencing (NGS). Processing was done as per protocol on the Ion Torrent S5 System for 1,210 samples and bioinformatics analysis was done. Results: Among the 1,210 samples tested, 762 (62.9%) were Delta/Delta-like and other lineages, 291 (24%) were Omicron, and 157 (12.9%) were invalid or repeat samples. Within a month, the proportion of Delta and other variants was reversed, 6% Omicron became 81%, and Delta and other variants became 19%, initially all Omicron cases were seen in international travelers and their contacts but soon community transmission was seen. The majority of patients with Omicron were asymptomatic (56.7%) or had mild disease (33%), 9.2% had moderate symptoms, and two (0.7%) had severe disease requiring hospitalization, of which one (0.3%) died and the rest were (99.7%) recovered. History of vaccination was seen in 81.1%, of the previous infection in 43.2% of cases. Among the Omicron cases, BA.1 (62.8%) was the predominant lineage followed by BA.2 (23.7%) and B.1.529 (13.4%), rising trends were seen initially for BA.1 and later for BA.2 also. Although 8.9% of patients with Delta lineage during that period were hospitalized, 7.2% required oxygen, and 0.9% died. To conclude, the community spread of Omicron occurred in a short time and became the predominant circulating variant; BA.1 was the predominant lineage detected. Most of the cases with Omicron were asymptomatic or had mild disease, and the mortality rate was very low as compared to Delta and other lineages.

Repurposing of FDA Approved Drugs Against SARS-CoV-2 Papain-Like Protease: Computational, Biochemical, and in vitro Studies.

The pandemic caused by SARS-CoV-2 (SCoV-2) has impacted the world in many ways and the virus continues to evolve and produce novel variants with the ability to cause frequent global outbreaks. Although the advent of the vaccines abated the global burden, they were not effective against all the variants of SCoV-2. This trend warrants shifting the focus on the development of small molecules targeting the crucial proteins of the viral replication machinery as effective therapeutic solutions. The PLpro is a crucial enzyme having multiple roles during the viral life cycle and is a well-established drug target. In this study, we identified 12 potential inhibitors of PLpro through virtual screening of the FDA-approved drug library. Docking and molecular dynamics simulation studies suggested that these molecules bind to the PLpro through multiple interactions. Further, IC50 values obtained from enzyme-inhibition assays affirm the stronger affinities of the identified molecules for the PLpro. Also, we demonstrated high structural conservation in the catalytic site of PLpro between SCoV-2 and Human Coronavirus 229E (HCoV-229E) through molecular modelling studies. Based on these similarities in PLpro structures and the resemblance in various signalling pathways for the two viruses, we propose that HCoV-229E is a suitable surrogate for SCoV-2 in drug-discovery studies. Validating our hypothesis, Mefloquine, which was effective against HCoV-229E, was found to be effective against SCoV-2 as well in cell-based assays. Overall, the present study demonstrated Mefloquine as a potential inhibitor of SCoV-2 PLpro and its antiviral activity against SCoV-2. Corroborating our findings, based on the in vitro virus inhibition assays, a recent study reported a prophylactic role for Mefloquine against SCoV-2. Accordingly, Mefloquine may further be investigated for its potential as a drug candidate for the treatment of COVID.

Genomic characterization unravelling the causative role of SARS-CoV-2 Delta variant of lineage B.1.617.2 in 2nd wave of COVID-19 pandemic in Chhattisgarh, India.

COVID-19 pandemic 2nd wave catastrophic effect in the state of Chhattisgarh, India, from where no exclusive genomic data yet published, has prompted us to undertake this study to unearth the causative variant. Whole-genome sequencing of SARS-CoV-2 isolated from COVID-19 infected nine vaccinated healthcare workers (HCW), thirty mild/moderate, seventeen severe, and twenty-seven deceased patients, was performed. The significant predominance of the SARS-CoV-2 variant of concern (VOC), Delta (lineage B.1.617.2) identified in sixty-four (77.1%) cases in contrast to B.1 and its sublineage in eleven (13.2%), variant under monitoring (VUM), Kappa (lineage B.1.617.1) in five (6.0%) and another VOC Alpha (lineage B.1.1.7) in three (3.6%) cases respectively (p < 0.05, χ2 = 162.49). 88.8% vaccine breakthrough, 60% mild/moderate, 94.4% severe and 81.5% dead patients were infected by Delta. Kappa presents exclusively in mild/moderate, Alpha in vaccine breakthrough, mild/moderate, and dead patient and B.1 and its sublineages in mild, severe, and dead patient categories. Delta variant spike mutation of T19R, G142D, E156G, L452R, and deletion (F157 and R158) helps in escaping antibody response, T478K and D614G enhance viral affinity with ACE2 receptor while P681R and D950N result in higher replication and transmissibility by cleaving S1/S2 at furin site. We conclude that Delta variant predominant role along with co-occurrence of Kappa, Alpha, and B.1 variant during COVID-19 2nd wave pandemic in Chhattisgarh may pose a potential threat of future outbreak through hybrid variant evolution. Thus, intensive genomic surveillance for monitoring variant evolution and a more efficacious vaccine against the Delta and Alpha variants are required.

The catalytic influence of phosphotungstic acid-functionalized Fe3O4 MNPs blended with TiO2 on the synthesis of novel spiro-acridines and the evaluation of their medicinal potential through molecular docking studies.

This manuscript describes an effective and rapid three-component synthesis of a novel series of spiro-acridine derivatives by integrating the pharmacologically dynamic hydantoin-phenytoin as the prime synthetic equivalent. The process was accelerated by Fe3O4@TiO2-PTA magnetic nanoparticles (MNPs), which acted as the heterogeneous catalytic system, under ultrasonic conditions. The reaction was performed in the green PEG-200 solvent under aerophilic conditions to obtain products with excellent yields. The characteristics of the synthesized magnetic nano-catalysts were corroborated through powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDAX), FT-IR, and VSM techniques. In addition, the structures of the synthesized compounds were ascertained on the basis of elemental analyses and spectro-analytical data (1H NMR, 13C NMR, and mass spectrometry). High yields, smaller E-factor, considerable atom economy, easy recovery, and recyclability of the catalyst and solvent are the captivating features of the developed protocol. Moreover, in view of the ongoing global research on COVID-19, herein, we tried to identify the potential sites of the synthesized moiety that can suitably fit the receptor sites of the main protease of SARS-CoV-2 (SARS-CoV-2 Mpro).