Covid-19 has caused worldwide devastation. IFIH1 is a pattern recognition receptor that senses coronavirus RNA and triggers interferon production as a first line of viral immune defense. The role of IFIH1 polymorphism, rs1990760 (C>T; aaA946T) in the epidemiology of viral infection is well studied, and the minor allele T resists viral infection. Knock-in mice with mutated IFIH1 protein (946T) for this allele have enhanced interferon production and protection from lethal viral infection. The minor allele frequency (Tmaf) varies widely from Africans (0.06 to 0.35) to Chinese (0.19 to 0.23) to Caucasians (0.56 to 0.69). During the initial days of infection when the social restrictions were not imposed, I show that the infection rate in Italy was lower as expected from its higher Tmaf (0.56) than that in China (Tmaf for southern China, 0.23). The infection rate in the USA and Spain was intermediate between those two countries despite higher Caucasian overall Tmaf (0.69), perhaps due to a more admixed African population in these countries. These analyses suggest that African-Americans and Chinese with low Tmaf of rs1990760 are more vulnerable to SARS-COV2 infection, apart from other genetic factors or socioeconomic conditions in these population. Taken together, an IFN-beta supplement might aid in preventing COVID-19 infection and help in development of herd immunity.

Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN in their lifetime, a large group of people is affected. Due to the complex nature of the disease, current diagnosis and treatment are not adequate to halt disease progression or provide an effective cure. DN is now considered a manifestation of inflammation where inflammatory molecules regulate most of the renal physiology. Recent advances in genetics and genomic technology have identified numerous susceptibility genes that are associated with DN, many of which have inflammatory functions. Based on their role in DN, we will discuss the current aspects of developing biomarkers and molecular therapy for advancing precision medicine.

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SARS-CoV2 virus is believed to be originated from a closely related bat Coronavirus RaTG13 lineage after gaining insertions of RBD of spike (S) protein by exchanged recombination with pangolin virus Pan_SL_COV_GD. SARSCoV2 uses its entry-point key residues in S1 protein to attach with human ACE2 receptor. SARS-CoV2 evolution comprises any of these possibilities: it entered human from bat with its poorly developed entry-point residues much before its known appearance with slower mutation rate; or recently with efficiently developed entry-point residues having more infective power with higher mutation rate; or through an intermediate host. RaTG13 has 96.3% identity with SARS-CoV2 genome implying that it substituted ~1106 nucleotides to evolute as present-day virus. Temporal analysis of SARS-CoV2 genome from December 2019 shows that its nucleotide substitution rate is as low as 27nt/year with an evolutionary rate of 9x10-4 /site/year, which is a little less than other retrovirus (10-4 to 10-6 /site/year). Estimation of TMRCA of SARS-CoV2 from bat RaTG13 lineage appears to be in between 9-14 years. Furthermore, evolution of a critical entry-point residue Y493Q needs two substitutions with an intermediate virus carrying Y493H (Y>H>Q), although such an intermediate virus has not been identified in known twenty-nine bat CoV virus. Genetic codon analysis indicates that SARS-CoV2 evolution from RaTG13 lineage strictly follows neutral evolution with strong purifying selection whereas its propagation in human disobeys neutral evolution as nonsynonymous mutations surpasses synonymous mutations with the increase of ω (dn/ds) signifying its proceedings towards divergent selection predictably for its infection power to evade multiple organs.