A network biology approach to identify crucial host targets for COVID-19.

The ongoing global pandemic of COVID-19, caused by SARS-CoV-2 has killed more than 5.9 million individuals out of ∼43 million confirmed infections. At present, several parts of the world are encountering the 3rd wave. Mass vaccination has been started in several countries but they are less likely to be broadly available for the current pandemic, repurposing of the existing drugs has drawn highest attention for an immediate solution. A recent publication has mapped the physical interactions of SARS-CoV-2 and human proteins by affinity-purification mass spectrometry (AP-MS) and identified 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Here, we taken a network biology approach and constructed a human protein-protein interaction network (PPIN) with the above SARS-CoV-2 targeted proteins. We utilized a combination of essential network centrality measures and functional properties of the human proteins to identify the critical human targets of SARS-CoV-2. Four human proteins, namely PRKACA, RHOA, CDK5RAP2, and CEP250 have emerged as the best therapeutic targets, of which PRKACA and CEP250 were also found by another group as potential candidates for drug targets in COVID-19. We further found candidate drugs/compounds, such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride that bind the target human proteins. The urgency to prevent the spread of infection and the death of diseased individuals has prompted the search for agents from the pool of approved drugs to repurpose them for COVID-19. Our results indicate that host targeting therapy with the repurposed drugs may be a useful strategy for the treatment of SARS-CoV-2 infection.

Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19.

BACKGROUND & OBJECTIVES: Healthcare workers (HCWs) are at an elevated risk of contracting COVID-19. While intense occupational exposure associated with aerosol-generating procedures underlines the necessity of using personal protective equipment (PPE) by HCWs, high-transmission efficiency of the causative agent [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] could also lead to infections beyond such settings. Hydroxychloroquine (HCQ), a repurposed antimalarial drug, was empirically recommended as prophylaxis by the National COVID-19 Task Force in India to cover such added risk. Against this background, the current investigation was carried out to identify the factors associated with SARS-CoV-2 infection among HCWs in the country. METHODS: A case-control design was adopted and participants were randomly drawn from the countrywide COVID-19 testing data portal maintained by the ICMR. The test results and contact details of HCWs, diagnosed as positive (cases) or negative (controls) for SARS-CoV-2 using real-time reverse transcription-polymerase chain reaction (qRT-PCR), were available from this database. A 20-item brief-questionnaire elicited information on place of work, procedures conducted and use of PPE. RESULTS: Compared to controls, cases were slightly older (34.7 vs. 33.5 yr) and had more males (58 vs. 50%). In multivariate analyses, HCWs performing endotracheal intubation had higher odds of being SARS-CoV-2 infected [adjusted odds ratio (AOR): 4.33, 95% confidence interval (CI): 1.16-16.07]. Consumption of four or more maintenance doses of HCQ was associated with a significant decline in the odds of getting infected (AOR: 0.44; 95% CI: 0.22-0.88); a dose-response relationship existed between frequency of exposure to HCQ and such reductions (χ[2] for trend=48.88; P <0.001). In addition, the use of PPE was independently associated with the reduction in odds of getting infected with SARS-CoV-2. INTERPRETATIONS & CONCLUSIONS: Until results of clinical trials for HCQ prophylaxis become available, this study provides actionable information for policymakers to protect HCWs at the forefront of COVID-19 response. The public health message of sustained intake of HCQ prophylaxis as well as appropriate PPE use need to be considered in conjunction with risk homoeostasis operating at individual levels.