International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Aug 2020
Synergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: What molecular dynamics studies of virus-host interactions reveal.
The emergence of SARS-coronavirus-2 (SARS-CoV-2) has led to a global pandemic disease referred to as coronavirus disease 19 (COVID-19). Hydroxychloroquine (CLQ-OH)/azithromycin (ATM) combination therapy is currently being tested for the treatment of COVID-19, with promising results. However, the molecular mechanism of action of this combination is not yet established. ⋯ This is consistent with a synergistic antiviral mechanism at the plasma membrane level, where therapeutic intervention is likely to be most efficient. This molecular mechanism may explain the beneficial effects of CLQ-OH/ATM combination therapy in patients with COVID-19. Incidentally, the data also indicate that the conserved Q-134/F-135/N-137 triad could be considered as a target for vaccine strategies.
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Int. J. Antimicrob. Agents · Aug 2020
Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a global public health emergency, and new therapeutics are needed. This article reports the potential drug target and mechanism of action of Arbidol (umifenovir) to treat coronavirus disease 2019 (COVID-19). Molecular dynamics and structural analysis were used to show how Arbidol targets the SARS-CoV-2 spike glycoprotein and impedes its trimerization, which is key for host cell adhesion and hijacking, indicating the potential of Arbidol to treat COVID-19. It is hoped that knowledge of the potential drug target and mechanism of action of Arbidol will help in the development of new therapeutics for SARS-CoV-2.
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Int. J. Antimicrob. Agents · Aug 2020
ReviewA review on possible modes of actions of Chloroquine/ Hydroxychloroquine: Repurposing against SAR-COV-2 (COVID 19) pandemic.
Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. ⋯ One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing.
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Int. J. Antimicrob. Agents · Aug 2020
ReviewCOVID-19 treatment: close to a cure? A rapid review of pharmacotherapies for the novel coronavirus (SARS-CoV-2).
Currently, there is no approved therapy for coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) therefore endorses supportive care only. However, frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China. ⋯ The efficacy of interferon is unclear owing to conflicting outcomes in coronavirus studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2, but studies on their clinical efficacy and whether the benefits outweigh the risk of dysrhythmias remain inconclusive. For patients who develop cytokine release syndrome, interleukin-6 inhibitors may be beneficial.
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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health threat. Although most patients with COVID-19 manifest fever and respiratory tract symptoms, SARS-CoV-2 infection may also involve other organs/systems and present with extra-respiratory manifestations, including cardiac, gastrointestinal, hepatic, renal, neurological, olfactory, gustatory, ocular, cutaneous and haematological symptoms. Occasionally, these extra-respiratory symptoms/signs represent the initial presentation of SARS-CoV-2 infection, prior to fever or respiratory manifestations. ⋯ Moreover, some extra-respiratory manifestations, such as ocular and gastrointestinal involvement, may be caused by direct invasion of SARS-CoV-2. Therefore, protective measures should be taken while managing the associated clinical specimens. Finally, several extra-respiratory manifestations, such as cardiac involvement, acute kidney injury, coagulation disorders and thrombotic complications, could be associated with a poor prognosis.