A Review on the New Indication of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in the Treatment of Coronavirus Disease ۲۰۱۹

BACKGROUND AND ABJECTIVEAn enzyme named reverse transcriptase is found in retroviruses, such as the human immunodeficiency virus (HIV), and produces DNA from the RNA template. This enzyme is inhibited by Nucleoside reverse transcriptase inhibitors (NRTIs). Hence, this class of antivirals is utilized to treat HIV and also HBV infections. These drugs inhibit virus replication via blocking reverse transcriptase. In this review, we discuss the interaction of this class of anti- HIV drugs with specific functional proteins and enzymes of SARS-CoV-۲.MATERIALS AND METHODSA search of the databases, including Web of Science, Embase, PubMed, Scopus, and Google Scholar, from commencement to September ۲۰۲۰ was done. The keywords include “SARS-CoV-۲,” “COVID-۱۹,” "Coronavirus," "Nucleoside reverse transcriptase inhibitors," "Tenofovir," "Emrtricitabine," "Zidovudine," "Stavudine," "Didanosine," "Lamivudine," and "Abacavir." Criteria for inclusion were clinical trials or observational studies regarding the effects of NRTIs on SARS-CoV-۲. Twenty-three articles were selected, including in vitro, in vivo, and clinical studies.RESULTS AND DISCUSSIONStudies showed that NRTIs could be effective against SARS-CoV-۲ through inhibition of RNA-dependent RNA polymerase (RdRp). Emtricitabine, zidovudine, and abacavir bind to target proteins, spike and Angiotensin-converting enzyme (ACE۲), with different binding energies. Didanosine is a promising drug in treating COVID-۱۹ by targeting Purine nucleoside phosphorylase (PNP). Didanosine exerts its anti-inflammatory action via inhibiting adenosine kinase function. Moreover, blockade of interleukin-۲ receptor by didanosine leads to a reduced immunologic response. Tenofovir was found to reduce the amount of inflammatory cytokines such as interleukin (Il)-۶, interferon, Il-۱۰, and monocyte chemoattractant protein-۱. Zidovudine as a potential therapy has a strong and stable interaction with nucleocapsid protein (N-protein).CONCLUSIONRdRp, spike, ACE۲, PNP, inflammatory cytokines, and nucleocapsid protein are involved in the pathogenesis of COVs. As discussed, NRTIs have potential mechanisms against SARSCoV-۲ by targeting these cytokines and proteins. However, it is important to prove their effectiveness in clinical trials.

کلیدواژه ها:

Coronavirus ، SARS-CoV-۲ ، COVID-۱۹ ، RdRp ، nucleoside reverse transcriptase inhibitors ، zidovudine