Antiviral activity of cationic amphiphilic drugs

Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Baritussio, Aldo; Palù, Giorgio

doi:10.1080/14787210.2017.1305888

Cited by 118 publications

(126 citation statements)

References 106 publications

(172 reference statements)

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“…8 Other mechanisms may include raise in endosomal pH in host cells thereby inhibiting auto-lysosome fusion and disrupting the enzymes needed for the viral replication. 9,10 Hydroxychloroquine (HCQ) is synthesized by N-hydroxyethyl side chain substitution of chloroquine. This modification renders HCQ more soluble than chloroquine which may confer advantage of relative lesser toxicity.…”

Section: Introductionmentioning

confidence: 99%

Review of Current Evidence of Hydroxychloroquine in Pharmacotherapy of COVID-19

Suranagi

Rehan

Goyal

2020

Preprint

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Purpose:The COVID-19 Pandemic has literally left the world breathless in the chase for Pharmacotherapy. With the vaccine approval likely more than a year away and novel drugs in early clinical trials, repurposing of existing drugs takes the center stage. A potential drug discussed both in geopolitical and global scientific community is hydroxychloroquine (HCQ). We intend to systematically weigh and analyze the existing evidence of HCQ in the light of published and pre-print data available so far. Methods: PubMed Ovid MEDLINE, EMBASE, Google scholar databases and official clinical trialRegistries of the United States, China, WHO ICTRP were electronically searched for studies for the use of HCQ in patients with COVID-19. Pre-proof article repositories like MedRxiv, BioRxiv, and ChemRxiv were also included in the search. The literature was critically appraised. Results:Total 71 articles were available as of 15 th April of which articles of relevance (three invitro studies, two open label non-randomized trials, two open label randomized control trials, one follow-up study, three reviews, ten short communications) and 88 clinical trials registered in three clinical trial registries were analyzed. HCQ seems to be efficient in inhibiting of SARS-CoV-2 in in-vitro cell lines; there is lack of strong evidence from human studies. Conclusions:The in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Currently literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of HCQ in COVID-19 prophylaxis and treatment, until robust evidence becomes available.

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Section: Introductionmentioning

confidence: 99%

Review of Current Evidence of Hydroxychloroquine in Pharmacotherapy of COVID-19

Suranagi

Rehan

Goyal

2020

Preprint

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“…To date, no commercial vaccines or specific therapies are available for EBOV. However, various studies have been reported that explain the comprehensive development of vaccines, small‐molecule inhibitors, and repurposed Food and Drug Administration (FDA) approved drugs against Ebola . Table provides an overview of anti‐EBOV compounds and their level of efficacy, reported in either IC 50 or EC 50 , in vitro assays against EBOV, clinical status, and observational studies.…”

Section: Introductionmentioning

confidence: 99%

Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

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Ebola virus disease (EVD), caused by Ebola viruses, resulted in more than 11 500 deaths according to a recent 2018 WHO report. With mortality rates up to 90%, it is nowadays one of the most deadly infectious diseases. However, no Food and Drug Administration‐approved Ebola drugs or vaccines are available yet with the mainstay of therapy being supportive care. The high fatality rate and absence of effective treatment or vaccination make Ebola virus a category‐A biothreat pathogen. Fortunately, a series of investigational countermeasures have been developed to control and prevent this global threat. This review summarizes the recent therapeutic advances and ongoing research progress from research and development to clinical trials in the development of small‐molecule antiviral drugs, small‐interference RNA molecules, phosphorodiamidate morpholino oligomers, full‐length monoclonal antibodies, and vaccines. Moreover, difficulties are highlighted in the search for effective countermeasures against EVD with additional focus on the interplay between available in silico prediction methods and their evidenced potential in antiviral drug discovery.

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“…From Table 2, adapted from Salata 2017 [32], it can be seen that commercially available cationic amphiphilic drugs screened for their antiviral activity often exhibit antiviral activity against different types or families of viruses, with similar IC 50 /EC 50 . It is possible that a number of agents from this list could also be active against the COVID-19 virus.…”

mentioning

confidence: 99%

Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses

Bleasel

Peterson

2020

Pharmaceuticals

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The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC 50 ) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC 50 concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC 50 s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.

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Antiviral activity of cationic amphiphilic drugs

Cited by 118 publications

References 106 publications

Review of Current Evidence of Hydroxychloroquine in Pharmacotherapy of COVID-19

Review of Current Evidence of Hydroxychloroquine in Pharmacotherapy of COVID-19

Perspectives towards antiviral drug discovery against Ebola virus

Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses

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