Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review

Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.

What is the role of microbial biotechnology and genetic engineering in medicine?

“…For example, nucleoside and nucleotide analogs such as Tenofovir, Sofosbuvir or Ribavirin are often used as antiviral drugs (Nishijima et al, 2019 ). Although the search for antivirals began with the successful isolation of small molecule‐based compounds from microorganisms, such as certain antibiotics, almost all of the antiviral drug therapies currently in use are of chemical origin (Holmes et al, 1981 ; Velásquez et al, 2024 ). The screening of compounds of natural origin often resulted in lower antiviral activities in vivo than in vitro or a very high degree of toxicity for therapeutic applications (El Sayed, 2000 ).…”

Unravelling Insights into the Evolution and Management of SARS-CoV-2

“…In addition, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins, and phenolics) with promising in vitro and in silico results for use in COVID-19 disease [158][159][160]. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin, and betulinic acid, which were proposed as SARS-CoV-2 inhibitors [159].…”

“…In addition, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins, and phenolics) with promising in vitro and in silico results for use in COVID-19 disease [158][159][160]. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin, and betulinic acid, which were proposed as SARS-CoV-2 inhibitors [159]. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2, and in vivo, a nebulised formulation has been demonstrated to alleviate the respiratory symptoms of COVID-19 [158,159,161].…”

RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 1 ] was identified in December 2019 as the cause of a respiratory illness designated coronavirus disease 2019 (COVID-19) [ 2 ]. Early in the pandemic, various new and repurposed antiviral drugs were considered as treatments for COVID-19 and evaluated in clinical trials, including remdesivir, favipiravir, azithromycin, hydroxychloroquine, and ritonavir, among others [ 3 , 4 ]. Remdesivir (Veklury), a combination of nirmatrelvir with ritonavir (Paxlovid), and molnupiravir (Lagevrio) have shown clinical efficacy in reducing mortality, the need for mechanical ventilation, and improving the clinical status of COVID-19 patients admitted to a hospital, and they are now commercially available through, e.g., patient assistance programs in the United States.…”