Viral Bad News Sent by EVAIL

Clauss, Matthias; Chelvanambi, Sarvesh; Cook, Christine M.; ElMergawy, Rabab; Dhillon, Navneet K.

doi:10.3390/v13061168

Cited by 6 publications

(2 citation statements)

References 105 publications

(121 reference statements)

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“…Furthermore, our pipeline can be adapted to a wide range of cell types including endothelial cells and monocytes. This is of interest since viruses including HIV and SARS-CoV-2 have been shown to specifically induce pulmonary endothelial cell activation ( 16 , 17 ). Our cell types of interest in the present study were epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

In silico Drug Screening Approach Using L1000-Based Connectivity Map and Its Application to COVID-19

Asano

Chelvanambi

Decano

et al. 2022

Front. Cardiovasc. Med.

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Conventional drug screening methods search for a limited number of small molecules that directly interact with the target protein. This process can be slow, cumbersome and has driven the need for developing new drug screening approaches to counter rapidly emerging diseases such as COVID-19. We propose a pipeline for drug repurposing combining in silico drug candidate identification followed by in vitro characterization of these candidates. We first identified a gene target of interest, the entry receptor for the SARS-CoV-2 virus, angiotensin converting enzyme 2 (ACE2). Next, we employed a gene expression profile database, L1000-based Connectivity Map to query gene expression patterns in lung epithelial cells, which act as the primary site of SARS-CoV-2 infection. Using gene expression profiles from 5 different lung epithelial cell lines, we computationally identified 17 small molecules that were predicted to decrease ACE2 expression. We further performed a streamlined validation in the normal human epithelial cell line BEAS-2B to demonstrate that these compounds can indeed decrease ACE2 surface expression and to profile cell health and viability upon drug treatment. This proposed pipeline combining in silico drug compound identification and in vitro expression and viability characterization in relevant cell types can aid in the repurposing of FDA-approved drugs to combat rapidly emerging diseases.

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Section: Discussionmentioning

confidence: 99%

In silico Drug Screening Approach Using L1000-Based Connectivity Map and Its Application to COVID-19

Asano

Chelvanambi

Decano

et al. 2022

Front. Cardiovasc. Med.

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“…It would be of particular interest to define the role of HIV Nef in CMV/HIV coinfection and risk for CVD in PWH on ART [20]. HIV Nef is linked to persistent dyslipidemia in PWH, which in turn contributes to the risk for CVD [21]. Intriguing evidence is mounting on the transfer of HIV Nef to endothelial cells and monocytes via extracellular vesicles, which could drive CVD [22].…”

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confidence: 99%

Cytomegalovirus: 40 years and still the major viral cofactor in HIV infection

Rinaldo¹

2022

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Obesity and age are transmission risk factors for SARS-CoV-2 infection among exposed individuals

Matamalas,

Chelvanambi,

Decano

et al. 2024

PNAS Nexus

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The coronavirus disease (COVID-19) pandemic has occurred in Massachusetts in multiple waves led by a series of emerging variants. While the evidence has linked obesity with severe symptoms of COVID-19, the effect of obesity on susceptibility to SARS-CoV-2 infection remains unclear. Identification of intrinsic factors, which increase the likelihood of exposed individuals succumbing to productive SARS-CoV-2 infection could help plan mitigation efforts to curb the illness. We aim to investigate whether obese individuals have a higher susceptibility to developing productive SARS-CoV-2 infection given comparable exposure to nonobese individuals. This case–control study leveraged data from the Mass General Brigham's (MGB) electronic medical records (EMR), containing 687,813 patients, to determine whether obesity at any age increases the proportion of infections. We used PCR results of 72,613 subjects who tested positive to SARS-CoV-2 or declared exposure to the virus independently of the result of the test. For this study, we defined susceptibility as the likelihood of testing positive upon suspected exposure. We demonstrate evidence that SARS-CoV-2 exposed obese individuals were more prone to become COVID positive than nonobese individuals [adjusted odds ratio = 1.34 (95% CI: 1.29–1.39)]. Temporal analysis showed significantly increased susceptibility in obese individuals across the duration of the pandemic in Massachusetts. Obese exposed individuals are at a higher risk of getting infected with SARS-CoV-2. This indicates that obesity is not only a risk factor for worsened outcomes but also increases the risk for infection upon exposure. Identifying such populations early will be crucial for curbing the spread of this infectious disease.

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Viral Bad News Sent by EVAIL

Cited by 6 publications

References 105 publications

In silico Drug Screening Approach Using L1000-Based Connectivity Map and Its Application to COVID-19

In silico Drug Screening Approach Using L1000-Based Connectivity Map and Its Application to COVID-19

Cytomegalovirus: 40 years and still the major viral cofactor in HIV infection

Obesity and age are transmission risk factors for SARS-CoV-2 infection among exposed individuals

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