Amodiaquine as COVID-19 Mpro Inhibitor: A Theoretical Study

Acharya, bnacharya

doi:10.26434/chemrxiv.12555137

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Additionally, amodiaquine present a synergic effect against viral replication of the SARS-CoV-2 in Vero E6 cells when it is combined with nelfinavir, and it presents higher synergic index when copared with other antimalarial drugs such as chloroquine, hydroxychloroquine, quinacrine and mefloquine (Ianevski et al, 2020). One theoretical pharmachophore modeling study published in Chemrxiv reinforces a possible action of this aminoquinoline inhibitor against the SARS-CoV-2 virus, with a mechanism of blocking its main protease with a theoretical Ki of 0.073 μM (Acharya, 2020).…”

Section: Discussionmentioning

confidence: 89%

Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review

et al. 2020

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The SARS-CoV-2 outbreak originally appeared in China in December 2019 and became a global pandemic in March 2020. This infectious disease has directly affected public health and the world economy. Several palliative therapeutic treatments and prophylaxis strategies have been used to control the progress of this viral infection, including pre-(PrEP) and post-exposure prophylaxis. On the other hand, research groups around the world are still studying novel drug prophylaxis and treatment using repurposing approaches, as well as vaccination options, which are in different pre-clinical and clinical testing phases. This systematic review evaluated 1,228 articles from the PubMed and Scopus indexing databases, following the Kitchenham bibliographic searching protocol, with the aim to list drug candidates, potentially approved to be used as new options for SARS-CoV-2 prophylaxis clinical trials and medical protocols. In searching protocol, we used the following keywords: “Covid-19 or SARS-CoV-2” or “Coronavirus or 2019 nCoV,” “prophylaxis,” “prophylactic,” “pre-exposure,” “COVID-19 or SARS-CoV-2 Chemoprophylaxis,” “repurposed,” “strategies,” “clinical,” “trials,” “anti-SARS-CoV-2,” “anti-covid-19,” “Antiviral,” “Therapy prevention in vitro,” in cells “and” human testing. After all protocol steps, we selected 60 articles that included: 15 studies with clinical data, 22 studies that used in vitro experiments, seven studies using animal models, and 18 studies performed with in silico experiments. Additionally, we included more 22 compounds between FDA approved drugs and drug-like like molecules, which were tested in large-scale screenings, as well as those repurposed approved drugs with new mechanism of actions. The drugs selected in this review can assist clinical studies and medical guidelines on the rational repurposing of known antiviral drugs for COVID-19 prophylaxis.

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Section: Discussionmentioning

confidence: 89%

Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review

et al. 2020

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show abstract

Section: Discussionmentioning

confidence: 89%

table2.xlsx

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Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19

et al. 2022

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In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. Despite a substantial number of clinical trials, drug repurposing did not deliver on its promise. While success was observed with some repurposed drugs (e.g., remdesivir, dexamethasone, tocilizumab, baricitinib), others failed to show clinical efficacy. One reason is the lack of clear translational processes based on adequate preclinical profiling before clinical evaluation. Combined with limitations of existing in vitro and in vivo models, there is a need for a systematic approach to urgent antiviral drug development in the context of a global pandemic. We implemented a methodology to test repurposed and experimental drugs to generate robust preclinical evidence for further clinical development. This translational drug development platform comprises in vitro, ex vivo, and in vivo models of SARS-CoV-2, along with pharmacokinetic modeling and simulation approaches to evaluate exposure levels in plasma and target organs. Here, we provide examples of identified repurposed antiviral drugs tested within our multidisciplinary collaboration to highlight lessons learned in urgent antiviral drug development during the COVID-19 pandemic. Our data confirm the importance of assessing in vitro and in vivo potency in multiple assays to boost the translatability of pre-clinical data. The value of pharmacokinetic modeling and simulations for compound prioritization is also discussed. We advocate the need for a standardized translational drug development platform for mild-to-moderate COVID-19 to generate preclinical evidence in support of clinical trials. We propose clear prerequisites for progression of drug candidates for repurposing into clinical trials. Further research is needed to gain a deeper understanding of the scope and limitations of the presented translational drug development platform.

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Amodiaquine as COVID-19 Mpro Inhibitor: A Theoretical Study

Cited by 3 publications

References 6 publications

Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review

Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review

table2.xlsx

Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19

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