<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

Abstract

The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.

Angiotensin System Polymorphisms’ in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study

“… 35 Moreover, patients with the D/D genotype show an increased mean pulmonary arterial pressure and vascular resistance after exercise, as compared to the remaining genotypes when treated with ACE inhibitors such as captopril. 14 A recent study performed comparing COVID-19 prevalence and rs1799752 allele frequency data, recovered by Johns Hopkins University and GnomAD, respectively, demonstrates that the ACE1 I/I genotype is significantly negatively correlated with susceptibility to SARS-CoV-2 infection and worse clinical outcome. 36 These results are in line with our data indicating that genotype I/I and allele I are significantly more frequent in the asymptomatic than symptomatic patient group ( Table 2 ).…”

“…The results of this study, albeit with a limited but well-selected number of patients, suggest that some gene variants of RAAS pathway could modulate some pathological conditions associated with the heterogeneous clinical picture caused by SARS-CoV-2 infection such as disseminated intravascular coagulation and thrombosis, interstitial pneumonia, conjunctivitis and the cytokine storm. 14 , 36 , 42 Furthermore, data would suggest that the early genetic evaluation of subjects infected with SARS-CoV-2 can predict the ongoing/severity of disease, becoming a useful tool for selecting those patients deserving more attention to avoid complications. This personalized approach (predictive medicine) might represent a step forward in the development of strategies to counteract this complicated pandemic situation, seriously affecting worldwide.…”

“… 12 The whole angiotensin system, including the angiotensin I-converting enzyme ( ACE1 ), the angiotensin-converting enzyme 2 ( ACE2 ), the angiotensinogen ( AGT ) and the receptors angiotensin II receptor type 1 ( AGTR1 ) were identified as the key factors for SARS-CoV-2 in entering into the cells, tissues and organs. 13 Based on our previous study concerning the potential application of a personalized approach in the selection of therapy for COVID patients, 14 we decided to evaluate whether six different Single Nucleotide polymorphisms (SNPs), pharmacogenetically relevant belonging to ACE1, ACE2, AGT and AGTR1 genes or their haplotype combinations, could be predictive of susceptibility to SARS-CoV-2 infection or could be related to the severity of disease. For this reason, we performed a pilot study analyzing the rs2074192 and rs2106809 ( ACE2 gene), rs1799752 ( ACE1 gene), rs4762 and rs699 ( AGT gene) and rs5186 ( AGTR1 gene) genetic variants in a selected population with SARS-CoV-2 infection clinically divided into asymptomatic and symptomatic groups.…”

Organoid and microfluidics-based platforms for drug screening in COVID-19

“…In this regard, the different frequencies of SNP alleles associated with toxicity or therapeutic responses to the most promising and repurposed drugs in patients with COVID-19 were recently described. [20]

Figure 1 Organoids as potential platforms for investigating the role of genetic background in coronavirus 2019 (COVID-19) pathogenesis. Genetic polymorphisms in three classes of gene, including receptors (a), HLAs (b) and other immune-related genes (c), might affect the susceptibility of individuals exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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Phacoemulsification and nucleic acid-enriched aerosol: considerations from an eye model of cataract simulation

“…A publication storm has been observed regarding studies on the coronavirus disease (COVID-19 pandemic) (March 11, 2020, WHO declaration), particularly focusing on acute respiratory syndrome coronavirus-2 (SARS-CoV-2) features, diagnosis, and therapies [ 1 – 3 ]. Of these studies, some reports highlight the aerosol-associated generating of the SARS-CoV-2 virus, mainly through respiratory droplets from infected subjects, including those, who are asymptomatic [ 4 – 6 ].…”