Respiratory viral pathogens like influenza and coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused outbreaks leading to millions of deaths. Vaccinations are, to date, the best and most economical way to control such outbreaks and have been highly successful for several pathogens. Currently used vaccines for respiratory viral pathogens are primarily live attenuated or inactivated and can risk reversion to virulence or confer inadequate immunity.

We report the detection of genomic signatures of giant viruses (GVs) in the metagenomes of three environment samples from Mumbai, India, namely, a pre-filter of a household water purifier, a sludge sample from wastewater treatment plant (WWTP), and a drying bed sample of the same WWTP. The de novo assembled contigs of each sample yielded 700 to 2000 maximum unique matches with the GV genomic database. In all three samples, the maximum number of reads aligned to Pandoraviridae, followed by Phycodnaviridae, Mimiviridae, Iridoviridae, and other Megaviruses. We also isolated GVs from every environmental sample (n = 20) we tested using co-culture of the sample with Acanthomoeba castellanii . From this, four randomly selected GVs were subjected to the genomic characterization that showed remarkable cladistic homology with the three GV families viz., Mimivirirdae ( Mimivirus Bombay [MVB]) , Megaviruses ( Powai lake megavirus [PLMV] and Bandra megavius [BAV]) , and Marseilleviridae ( Kurlavirus [KV]) . All 4 isolates exhibited remarkable genomic identity with respective GV families. Functionally, the genomes were indistinguishable from other previously reported GVs, encoding nearly all COGs across extant family members. Further, the uncanny genomic homogeneity exhibited by individual GV families across distant geographies indicate their yet to be ascertained ecological significance.

No abstract

The COVID-19 pandemic has highlighted the need for novel antivirals for pandemic management and preparedness. Targeting host processes that are co-opted by viruses is an attractive strategy for developing antivirals with a high resistance barrier. Picolinic acid (PA) is a byproduct of tryptophan metabolism, endogenously produced in humans and other mammals. Here we report broad-spectrum antiviral effects of PA against enveloped viruses, including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), Influenza A virus (IAV), Flaviviruses, Herpes Simplex Virus, and Human Parainfluenza Virus. We further demonstrate using animal models that PA is effective against SARS-CoV-2 and IAV, especially as an oral prophylactic. The mode of action studies revealed that PA inhibits viral entry of enveloped viruses, primarily by interfering with viral-cellular membrane fusion, inhibiting virus-mediated syncytia formation, and dysregulating cellular endocytosis. Overall, our data establish PA as a broad-spectrum antiviral agent, with promising preclinical efficacy against pandemic viruses SARS-CoV-2 and IAV.