Two years into COVID‐19 – Lessons in SARS‐CoV‐2 and a perspective from papers in <i>FEBS Letters</i>

Greber, Urs F.

doi:10.1002/1873-3468.14226

Cited by 6 publications

(6 citation statements)

References 57 publications

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“…It has anti-viral effects against SARS-CoV-2 in hamsters ( Driouich et al, 2021 ), and is in clinical trials against COVID-19 ( Joshi et al, 2021 ). A recent high-throughput computational protein design protocol identified mutational hotspots in the SARS-CoV-2 RNA polymerase confering favipiravir resistance, and remarkably some of these mutations already exist in SARS-CoV-2 genomes circulating in humans ( Padhi et al, 2021 ; Greber, 2021 ). This implies that direct anti-viral agents readily face drug-resistant viruses, even before treatment, and likely have limited therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern

Murer¹,

Volle²,

Andriasyan³

et al. 2022

Current Research in Virological Science

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Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with oral availability. Methylene blue (MB, used for the treatment of methemoglobinemia), Mycophenolic acid (MPA, used in organ transplantation) and the anti-fungal agent Posaconazole (POS) had the broadest anti-CoV spectrum. They inhibited the shedding of SARS-CoV-2 and variants-of-concern (alpha, beta, gamma, delta) from HAEEC in either pre- or post exposure regimens at clinically relevant concentrations. Co-treatment of cultured cells with MB and the FDA-approved SARS-CoV-2 RNA-polymerase inhibitor Remdesivir reduced the effective anti-viral concentrations of MB by 2-fold, and Remdesivir by 4 to 10-fold, indicated by BLISS independence synergy modelling. Neither MB, nor MPA, nor POS affected the cell delivery of SARS-CoV-2 or OC43 (+)sense RNA, but blocked subsequent viral RNA accumulation in cells. Unlike Remdesivir, MB, MPA or POS did not reduce the release of viral RNA in post exposure regimen, thus indicating infection inhibition at a post-replicating step as well. In summary, the data emphasize the power of unbiased, full cycle compound screens to identify and repurpose broadly acting drugs against coronaviruses.

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Section: Discussionmentioning

confidence: 99%

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern

Murer¹,

Volle²,

Andriasyan³

et al. 2022

Current Research in Virological Science

Self Cite

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“…There exists other functional mutations which can give rise to drug resistance. Therefore, screening the mutations to understand and manage the mechanisms of SARS-CoV-2 drug resistance is imperative to find viable drug target candidates for designing effective antiviral drugs [38][39][40]. Also, functional mutations can impact the results of diagnostic tests and lead to false-negative using rapid antigen tests.…”

Section: Discussionmentioning

confidence: 99%

SARS2Mutant: SARS-CoV-2 Amino-Acid Mutation Atlas Database

Rahimian

Mahmanzar

Mahdavi

et al. 2022

Preprint

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The coronavirus disease 19 (COVID-19) is a highly pathogenic viral infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the global pandemic of 2020.A lack of therapeutic and preventive approaches including drugs and vaccines, has quickly posed significant threats to world health. A comprehensive understanding of the evolution and natural selection of SARS-CoV-2 against the host interaction and symptoms at the phenotype level could impact the candidate's strategies for the fight against this virus. SARS-CoV-2 Mutation (SARS2Mutant, http://sars2mutant.com/) is a database that provides comprehensive analysis results based on tens of thousands of high-coverage and high-quality SARS-CoV-2 complete protein sequences. The structure of this database is designed to allow the users to search for the three different strategies among amino acid substitution mutations based on gene name, geographical zone or comparative analysis. Based on each strategy, five data types are available to the user: mutated sample frequencies, heat map of the mutated amino acid positions, timeline trend for mutation survivals and natural selections, and charts of changed amino acids and their frequencies. Due to the increase of virus protein sequence samples published daily showing the latest trends of current results, all sequences in the database are reanalyzed and updated monthly. The SARS-2Mutant database provides current analysis and updated data of mutation patterns and conserved regions, helpful in developing and designing targeted vaccines, primers and drug discoveries.

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“…The S protein is essential for virus binding to the host cell, entry, and infection [ 2 , 77 , 78 , 81 ]. SARS-CoV-2 and SARS-CoV are similar in their pathology, both binding to angiotensin-converting enzyme 2 (ACE2) receptor but have distinct transmission efficacy [ 78 , 82 ]. After docking to ACE2, the virus is processed by cellular transmembrane protease serine (TMPRSS2), which cleaves ACE2 and activates the S protein, facilitating virus entry into the host cell [ 2 , 83 ].…”

Section: Human Coronaviruses and Infection Cyclementioning

confidence: 99%

Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs

et al. 2022

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Although COVID-19 is primarily a respiratory disease, it may affect also the cardiovascular system. COVID-19 patients with cardiovascular disorder (CVD) develop a more severe disease course with a significantly higher mortality rate than non-CVD patients. A common denominator of CVD is the dysfunction of endothelial cells (ECs), increased vascular permeability, endothelial-to-mesenchymal transition, coagulation, and inflammation. It has been assumed that clinical complications in COVID-19 patients suffering from CVD are caused by SARS-CoV-2 infection of ECs through the angiotensin-converting enzyme 2 (ACE2) receptor and the cellular transmembrane protease serine 2 (TMPRSS2) and the consequent dysfunction of the infected vascular cells. Meanwhile, other factors associated with SARS-CoV-2 entry into the host cells have been described, including disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), the C-type lectin CD209L or heparan sulfate proteoglycans (HSPG). Here, we discuss the current data about the putative entry of SARS-CoV-2 into endothelial and smooth muscle cells. Furthermore, we highlight the potential role of long non-coding RNAs (lncRNAs) affecting vascular permeability in CVD, a process that might exacerbate disease in COVID-19 patients.

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Two years into COVID‐19 – Lessons in SARS‐CoV‐2 and a perspective from papers in FEBS Letters

Cited by 6 publications

References 57 publications

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern

SARS2Mutant: SARS-CoV-2 Amino-Acid Mutation Atlas Database

Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs

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