Latest preprints

The recent SARS-CoV-2 pandemic has witnessed the emergence of various virus variants. While the phenomenon of immunity-evading variants is known in other viruses like influenza, there is limited understanding of the ecological and evolutionary processes involved in this succession. Due to the availability of large-scale epidemiological data collected and shared publicly during the Covid-19 pandemic, it becomes possible to explore evolutionary questions that also have implications for public health. We propose multiple alternative hypotheses regarding the origin and spread of these variants and evaluate them based on epidemiological data. Our analysis indicates that the invasion of novel variants is primarily limited by selection rather than mutation. Moreover, the repeated waves observed during the pandemic are not solely caused by the emergence of new variants. Instead, there is a significant overlap between conditions that lead to a wave and those that favor the selection of partially immune-evading variants. This association may contribute to the rise of a new wave alongside the invasion of a new variant. However, the association is not strong enough to support a causal role of the new variant. The dynamic interplay between epidemiological processes and selection on viral variants carries important implications for public health and can guide future policies aimed at effectively controlling infectious epidemics.

The cytosolic PRRs and Cyclic GMP-AMP synthase (cGAS) attain the capability to detect DNA viruses like, vaccinia virus, HSV1 and HSV2, cytomegalovirus, adenoviruses, human papilloma virus etc and clear them off via IFN I regulations. PRRs can recognize the pathogen associated molecular patterns- PAMPs and self-DNA in the form of damage associated molecular patterns- DAMPs under stressed conditions, when monocytes and macrophages with other immune cells release excessive proinflammatory cytokines. Cytotoxic ssDNA and dsDNA escape from endosome and rupture mitochondrial DNA as well. The cGAS-STING signaling also have the polymorphic role to increase the pathogenesis in case of positive sense RNA virus’s infection (SARSCoV-2), retroviruses and bacterial pathogens. STING protein is primarily present on ER, mitochondrial and Golgi bodies and gets activated through ligands cGAS / or cGAMP (2’-3’-cGAMP). This specific molecular pathway triggers the innate immune response in the cytoplasm and consecutively develop the adaptive immune arm against the pathogens. Activation of cGAS-STING signaling also exerts the antitumor effects via activation of p53 and p16 proteins. TLR9 is expressed on the DCs and B-cells to detect CpG motif of DNA. PRR agonists activate the STING to work effectively on CD4+ and CD8+ cells to establish the sustainable innate & adaptive immune response. STING also harbours the adjuvant properties to release potent immune response in the development of novel therapeutics against cancer, autoimmune and infectious diseases.

Elucidating ancestor-descendant relationships of viral lineages is crucial for addressing the question of when and where a virulent viral strain originated. The D614G clade, with an Aspartate-614 to Glycine (D614G) mutation, includes all recent variants of SARS-CoV-2 and tend to be more infectious than the viral strains isolated in Wuhan. The D614G clade is characterized by TTTG at four nucleotide sites (sites 241, 3037, 14408 and 23403 following the reference genome NC_045512), in contrast to CCCA shared among early SARS-CoV-2 genomes sampled in China and those that can be traced to China. It was believed that the TTTG lineage descended from the early viral CCCA lineages. A set of SARS-CoV-2 sequences collected from Sept. 12 to Dec. 18, 2019, in Lombardy, Milan and Turin in Italy provided, for the first time, strong evidence that the D614G/TTTG lineage has already been circulating in Italy in 2019. I discussed extensively the controversies arising from this set of early SARS-CoV-2 sequences.

Five-day-old mouse pups were fed either Prevnar 13 alone or peripheral blood mononuclear cells (PBMCs) isolated from adult donors and pulsed ex vivo with Prevnar-13. Mice vaccinated with Prevnar-13 or with vaccine-pulsed PBMCs displayed a positive serum IgM response greater than that of mice treated with mock-pulsed PBMCs, though the response of Prevnar-13-treated vs. Prevnar 13-pulsed PMBC-treated groups was not significantly different. However, neither group was protected against lethal infectious challenge. We conclude that it is possible to elicit a neonatal immunological response after vaccine or vaccine-pulsed PBMCs administered via the oral route, but a single dose is insufficient to protect against subsequent infection. Further studies can confirm whether a booster dose may improve protective efficacy and may reveal a difference between vaccine-pulsed PBMC treatment and vaccine alone that is not apparent after a single dose.

The rapidly increasing rate of antimicrobial drug resistance requires novel ways of treating infections. Harnessing the synergistic effect of the combined use of conventional antibiotics with naturally occurring antimicrobial substances is an emerging frontier in the fight against the spread of antimicrobial resistance. Synergy is measured by using the fractional inhibitory concentration index (FICI). Saponins are secondary metabolites produced by plants and they help defend the plant against natural stressors. This article aims to review the synergistic activity of saponins with traditional antibiotics. Thirteen plants were included in the final review, out of which eight species showed a FICI score below 0.5 (synergistic). These were Jatropha curcas, Melanthera elliptica, Glycine max, Tribulus terrestris, Salvia officinialis, Spergulara marginata, Paromychia argenetea, and Syzigium aromaticum. The highest degree of synergy was observed against S. aureus with the combined use of Jatropha curcas and rifampicin (FICI 0.04), Melanthera elliptica and tetracycline (0.05), and Glycine max and benzylpenicillin (0.22). In addition, a high degree of synergy against E. coli was observed with the combined use of Melanthera elliptica and tetracycline (0.07), Jatropha curcas and rifampicin (0.08), Salvia officinialis and amoxicillin (0.38).

Vegetables are frequently consumed by people all over the world and hence, the microbiological quality of vegetable especially fresh produces are of significance for the sake of public health sustainability. Vegetables are spoiled by a range of microorganisms including bacteria and fungi. Among the bacterial species, Corynebacterium, Pseudomonas spp., Listeria monocytogenes, Clostridium botulinum, Erwinia carotovora, and Xanthomonas campestris are the common vegetable spoilage microorganisms while the fungal genera Botrytis cinerea, Colletotrichum, Aspergillus, Alternaria, Cladosporium, Fusarium, Penicillium, and Rhizopus spp. are the prominent spoiling candidates. Understanding vegetable spoilage mechanism/ microbial pathogenesis is important. The harvesting and handling procedures, storage conditions of vegetables, processing, injury of the vegetable plant tissues, and plant resistance against the pathogens are also of significance in order to analyze the toxic metabolites in the affected sites within the vegetables as well as for the prediction of the foodborne illness outbreaks. Implementation of good agricultural practices (GAPs) and good manufacturing practices (GMPs) during vegetable cultivation, harvesting, sorting, storage, transportation, and distribution is important. Moreover, processing of vegetables prior to consumption; i.e., controlling contamination of microbes, a thorough wash with vinegar water, salt water, and other washing means are important preventive measures to ensure the prevention of microbial contamination. Furthermore, up-to-date knowledge on the vegetable spoiling microorganisms, the epidemiology of such microbial contamination, and possible sources and route of the contamination may attribute to the possible future perspective on food safety.

Objectives. This study was aimed to investigate if canine parvovirus is infecting domestic cat populations in Mexico and determine the presence of different antigenic types of this virus affecting both healthy cats and cats with gastroenteritis.Methods. Seventy-five cats were studied, 25 with gastroenteritis and 50 healthy, viral DNA was extracted, a stool sample from each cat was obtained using rectal swabs, 100 ng of DNA from each sample were used for the PCR reaction, cats positive for CPV-2 were identified utilizing this method, only samples of positive animals were amplified to obtain a complete sequence of VP2 gen and identified an antigenic type of CPV-2 infecting the cats.Results. 60% of the cats with gastroenteritis and 22% of healthy cats were positive for Canine parvovirus; the variant 2c only was identified in healthy cats, while ten cats with gastroenteritis were infected by canine parvovirus 2a and type 2c. Conclusions and relevance. This is the first report about variants of CPV-2 circulating in Mexican cats healthy and with gastroenteritis. The identification of canine parvovirus infection in cats is important because infected cats may contribute to the transmission of the disease to cats and dogs populations.