3(4)-40 other hand, fragile X mental retardation protein (FMRP), the product of FMR1 gene, was demonstrated to target influenza and Zika viruses, while metabotropic glutamate 5 receptor (mGluR5) inhibitors, commonly utilized in FXS, often ameliorate SARS-CoV-2 symptoms, indicating a two-way street between viral infections and TRDs [13][14][15].Recent studies have reported that STRs can increase the risk of schizophrenia and autism spectrum disorder (ASD), indicating that these sequences play a major role not only in monogenic but also in polygenic disorders [16,17]. Indeed, the findings of Ambati BK, et al. are in line with our own studies that connected FCS to pathological cell-cell fusion, neurodegeneration, and psychopathology [18,19]. As COVID-19 mRNA vaccines elicit the expression of full-length S antigen (including the FCS), these therapeutics may promote pathological syncytia [20]. Along this line, giant cell myocarditis and arteritis due to pathological cell-cell fusion were recorded in Vaccine Adverse Event Reporting System (VAERS) [21,22].Pfizer and Moderna COVID-19 messenger RNA (mRNA) vaccines are heavily engineered to facilitate translation and improve stability, modifications that include codon optimization enriched with CG repeats [6]. However, as MSH3 regulates STRs, including the CG repetitions, vaccine efficacy is likely enhanced by the inhibition or attenuation of this protein. This may explain the reason Moderna was interested in patenting this molecule in 2016. In addition, as COVID-19 mRNA therapeutics encode the entire S antigen, MSH3may be over expressed, a phenomenon associated with loss of function [23]. Indeed, MSH3 may be inactivated via promoter methylation or over expression [24].From the neuropsychiatric perspective, the novel MSH3 findings are significant as this protein, encoded on chromosome 5 (q11-q13), shares a common promoter with dihydrofolate reductase (DHFR), a gene disrupted in many neuropsychiatric conditions, including ASDs, schizophrenia, depressive and bipolar disorder as well as immune dysfunction, diabetes, type I, and epilepsy [25][26][27][28][29][30][31]. Due to the common promoter, vaccine-induced MSH3 inhibition likely attenuates DHFR, predisposing to these pathologies. In favor of this statement, we bring the fact that treatment with methotrexate, a DHFR inhibitor, was associated with neuropsychiatric pathology, including anxiety, depression, suicidal behavior, and dementia [16], [32-36].Taken together, the MSH3/DHFR locus may represent a hub where immunity, metabolism, and neuropsychiatric pathology intersect, therefore a better understanding of these genes would shed light on the etiopathogenesis of these conditions.

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We read with great interest the paper by Beaudoin CA et al. "Are There Hidden Genes in DNA/RNA Vaccines?", reporting overlapping sequences between the SARS-CoV-2 spike (S) glycoprotein and two viral genes [1]. If translated, the undesired proteins may cause rare, untoward effects, including those recorded in Vaccine Adverse Event Reporting System (VAERS).These findings are in line with our own research and that of others however, aside from overlapping genes (OLGs), the S protein also contains overlapping molecular structures and signals (heptad repeats, simple sequence repeats, calcium calmodulin kinase II, and prion-like domains) that can lead to VAERS-recorded pathology [2-6].