Abstract:In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. On March 15, 2020, a stay-at-home order was put into effect in the state of Massachusetts, USA, to flatten the curve of the spread of the novel SARS-CoV2 virus that causes COVID-19. For biomedical researchers in our state, this meant putting a hold on experiments for nine weeks until May 18, 2020. To keep the lab engaged and productiv… Show more
“…2 A). Zhang and coworkers 23 suggested that the ORF8 protein is able to interfere with the antigen presentation, affecting the process of recognition and elimination of the virus by cytotoxic T cells. Figure 2 ORF8 protein and its interaction with MHC-I.…”
Section: Resultsmentioning
confidence: 99%
“…ORF6 displays a critical antagonistic activity, avoiding the antiviral innate immune response, inhibiting interferon β (IFN-β) production and blocking the expression of STAT1-activated genes to SARS-CoV 20 , 49 . ORF8 has been considered one of the most relevant proteins related to viral replication in humans, as it is able to inhibit the expression of IFN- β 20 , 50 . The SARS-CoV-2 N protein acts as an IFN-I antagonist regulating the synthesis and signaling of this route.…”
Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, contributing towards studies of selective structure-based drug discovery and vaccine development.
“…2 A). Zhang and coworkers 23 suggested that the ORF8 protein is able to interfere with the antigen presentation, affecting the process of recognition and elimination of the virus by cytotoxic T cells. Figure 2 ORF8 protein and its interaction with MHC-I.…”
Section: Resultsmentioning
confidence: 99%
“…ORF6 displays a critical antagonistic activity, avoiding the antiviral innate immune response, inhibiting interferon β (IFN-β) production and blocking the expression of STAT1-activated genes to SARS-CoV 20 , 49 . ORF8 has been considered one of the most relevant proteins related to viral replication in humans, as it is able to inhibit the expression of IFN- β 20 , 50 . The SARS-CoV-2 N protein acts as an IFN-I antagonist regulating the synthesis and signaling of this route.…”
Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, contributing towards studies of selective structure-based drug discovery and vaccine development.
“…The precise anti-viral mechanism of teicoplanin has also not been determined. It has however been suggested that teicoplanin potently block the entry of SARS-CoV-2 through the inhibition of the enzymatic activity of cathepsin L [ 43 ]. Based on this, the authors recommended the use of teicoplanin in both prophylaxis and therapeutic management of patients with SARS-CoV-2 infection [ 43 ].…”
Background
Drug repurposing otherwise known as drug repositioning or drug re-profiling is a time-tested approach in drug discovery through which new medical uses are being established for already known drugs. Antibiotics are among the pharmacological agents being investigated for potential anti-SARS-COV-2 activities. The antibiotics are used either to resolve bacterial infections co-existing with COVID-19 infections or exploitation of their potential antiviral activities. Herein, we aimed to review the various antibiotics that have been repositioned for the management of COVID-19.
Methods
This literature review was conducted from a methodical search on PubMed and Web of Science regarding antibiotics used in patients with COVID-19 up to July 5, 2020.
Results
Macrolide and specifically azithromycin is the most common antibiotic used in the clinical management of COVID-19. The other antibiotics used in COVID-19 includes teicoplanin, clarithromycin, doxycycline, tetracyclines, levofloxacin, moxifloxacin, ciprofloxacin, and cefuroxime. In patients with COVID-19, antibiotics are used for their immune-modulating, anti-inflammatory, and antiviral properties. The precise antiviral mechanism of most of these antibiotics has not been determined. Moreover, the use of some of these antibiotics against SARS-CoV-2 infection remains highly controversial and not widely accepted.
Conclusion
The heavy use of antibiotics during the COVID-19 pandemic would likely worsen antibiotic resistance crisis. Consequently, antibiotic stewardship should be strengthened in order to prevent the impacts of COVID-19 on the antibiotic resistance crisis.
“…However, given that there are different mutations across the different emerging SARS-CoV-2 variants, vaccines were found to be effective against all these mutations. As such, the Pfizer-BioNtech BNT162b2 vaccine has successfully induced neutralisation against the panel of the aforementioned spike protein mutations across different SARS-CoV-2 variants [ 55 ].…”
Section: Comparative Analysis Of Different Coronavirus and Sars-cov-2mentioning
confidence: 99%
“…Other SARS-CoV-2 variances (B.1.1.7, B.1.351 & P.1) have also shown various spike protein mutations (N501Y, P681H, K417N, E484K and K417T), in which enhances the binding affinity of S protein for ACE-2 receptor at a greater extent [ 51 – 55 ]…”
Section: Comparative Analysis Of Different Coronavirus and Sars-cov-2mentioning
The Coronavirus Disease 2019 (COVID-19), a pneumonic disease caused by the SARS Coronavirus 2 (SARS-CoV-2), is the 7th Coronavirus to have successfully infected and caused an outbreak in humans. Genome comparisons have shown that previous isolates, the SARS-related coronavirus (SARSr-CoV), including the SARS-CoV are closely related, yet different in disease manifestation. Several explanations were suggested for the undetermined origin of SARS-CoV-2, in particular, bats, avian and Malayan pangolins as reservoir hosts, owing to the high genetic similarity. The general morphology and structure of all these viral isolates overlap with analogous disease symptoms such as fever, dry cough, fatigue, dyspnoea and headache, very similar to the current SARS-CoV-2. Chest CT scans for SARS-CoV-2, SARS-CoV and MERS-CoV reveal pulmonary lesions, bilateral ground-glass opacities, and segmental consolidation in the lungs, a common pathological trait. With greatly overlapping similarities among the previous coronavirus, the SARS-CoV, it becomes interesting to observe marked differences in disease severity of the SARS-CoV-2 thereby imparting it the ability to rapidly transmit, exhibit greater stability, bypass innate host defences, and increasingly adapt to their new host thereby resulting in the current pandemic. The most recent B.1.1.7, B.1.351 and P.1 variants of SARS-CoV-2, highlight the fact that changes in amino acids in the Spike protein can contribute to enhanced infection and transmission efficiency. This review covers a comparative analysis of previous coronavirus outbreaks and highlights the differences and similarities among different coronaviruses, including the most recent isolates that have evolved to become easily transmissible with higher replication efficiency in humans.
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