Repurposing of well-known medications as antivirals: hydroxychloroquine and chloroquine – from HIV-1 infection to COVID-19

ABSTRACT

Introduction

Chloroquine (CQ) and hydroxychloroquine (HCQ) originally were prescribed for prevention or treatment of malaria, but now successfully are used in several rheumatologic diseases. In addition, in recent decades considering their immunomodulatory effects, high tolerably, and low cost, they are evaluated for various viral infections from HIV to COVID-19.

Areas covered

In this review, we tried to summarize all available studies on HCQ and CQ efficacy for management of viral infections and the probable mechanisms of action. The data were collected by searching ‘Hydroxychloroquine,’ ‘Chloroquine,’ ‘Viral infection,’ and names of various viral infections in PubMed/MEDLINE, Scopus, and Google Scholar databases from commencement to June 2020. Out of 95 search results, 74 most relevant works were gathered.

Expert opinion

HCQ/CQ showed acceptable efficacy in HIV especially as an adjuvant treatment beside routine HAART. However, for some viral infections such as ZIKA, EBOLA, SARS-CoV, and MERS-CoV, human studies are lacking. In the COVID-19 pandemic, in vitro and preliminary human studies showed encouraging findings. However, later well-designed trials and retrospective studies with large sample size not only reported non-significant efficacy but also showed more cardiac adverse reactions. Alkalinization of acid vesicles is the most important mechanism of action.

KEYWORDS:

• Hydroxychloroquine
• Chloroquine
• viral infection
• HIV
• Covid-19

Article highlights

• HCQ and CQ showed acceptable efficacy especially as an adjuvant treatment beside routine highly active antiretroviral therapy (HAART) in HIV infection.

• For some viral infections like ZIKA, EBOLA, Severe acute respiratory syndrome coronavirus (SARS-CoV) & Middle East respiratory syndrome coronavirus (MERS-CoV), despite promising efficacy in pre-clinical studies, human trials are lacking.

• In the most recent coronavirus pandemic, COVID-19, in vitro and preliminary human studies on anti-malarial agents showed encouraging efficacy. However, later well-designed clinical trials and retrospective or observational studies with large sample size not only reported non-significant usefulness but also showed more cardiac adverse reaction, like QT prolongation.

• The most important antimalarial agents’ mechanisms of action in viral infections could be summarized as follows: alkalinization of endosomal/lysosomal/golgi vesicles resulting from the accumulation of weak base, inhibition of viral attachment, entry, and maturation with various mechanisms, and anti-inflammatory and anti-thrombotic mechanisms.

• CQ/HCQ may be suitable options for prevention of some viral infections vertical transmission during pregnancy and also for increasing vaccination efficacy based on some available data.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.