https://orcid.org/0000-0002-9200-5698
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.
Abbreviations
ABC, Abacavir; ACE2, Angiotensin-converting enzyme 2; ALP, Alkaline phosphatase; ARDS, Acute respiratory distress syndrome; ATV, Atorvastatin; AZT, Zidovudine; CDC, Centers for Disease Control and Prevention; COVID19, Coronavirus disease 2019; CQ, Chloroquine; CRP, C-reactive protein; ER, Endoplasmic reticulum; ERGIC, Reticulum-Golgi intermediate compartment; FDA, Food and Drug Administration; HBV, Hepatitis B virus; HCQ, Hydroxychloroquine; HIV, Human immunodeficiency virus; ICU, Intensive care unit; IVM, Ivermectin; Kd, Dissociation constant; Ki, Inhibition constant; LDH, Lactate dehydrogenase; LH, Lianhuaqingwen; MERS-CoV, Middle East respiratory syndrome coronavirus; Mpro, Main protease; NRF2, Nuclear factor erythroid; Nsps, Non-structural proteins; PBECs, Primary bronchial epithelial cells; PBMC, Peripheral blood mononuclear cells; PL pro, Papain-like protease; PoPEx, Pomegranate peel extract; P2Et, Extract of Caesalpinia spinosa; RBD, Receptor-binding domain; RdRP, RNA-dependent RNA polymerase; RMP, Remdesivir monophosphate; RT, Reverse transcriptase; RTC, Replication and transcription complex; SARS-CoV, Severe acute respiratory syndrome coronavirus; SARS-CoV-2, Severe acute respiratory syndrome Coronavirus 2; S protein, Spike protein; TMPRSS2, Transmembrane serine protease 2; VitD, Vitamin D; VTE, Venous thromboembolism; WHO, World Health Organization; 3CL pro, Chymotrypsin-like protease.
Disclosure
The authors report no conflicts of interest in this work.