An overview of potential therapeutic agents to treat COVID-19

Abstract

Since China first reported an unusual type of pneumonia on December 31, 2019, the number of people identified with this pneumonia has been increasing at an alarming rate, leading to a worldwide public health emergency. This new infectious disease, officially named coronavirus disease (COVID-19) on February 11, 2020 by the World Health Organization (WHO), is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On March 11, 2020, the COVID-19 outbreak was officially declared a pandemic by the WHO. The disease is characterized by flu-like symptoms, such as cough, fever, myalgia, and fatigue. Although some infections are asymptomatic, many patients develop pneumonia, and some patients even develop severe and fatal respiratory diseases. As noted by the WHO, a total of 32,029,704 confirmed cases and 979,212 deaths worldwide were caused by COVID-19 as of September 25, 2020 (1). Nevertheless, there are no approved vaccines or specific drugs available for the prevention and treatment of COVID-19 at this moment. Given the threat of the pandemic and urgent need for effective vaccines and antivirals, vigorous efforts are being made globally to stop the COVID-19 epidemic. Compared to de novo drug development, drug repurposing offers advantages in taking less time and involving less cost, so it may be an ideal strategy for finding and identifying effective and safe potential therapeutic agents for the disease (2). A better understanding of SARS-CoV-2 virology, the underlying mechanisms by which it attacks host cells, and the host response to the infection is crucial to drug discovery and repurposing. Like severe acute respiratory syndrome coronavirus (SARS-CoV) that emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) that was identified in 2012, SARS-CoV-2 is a lipid-enveloped, single-stranded, positive sense RNA virus that is a zoonotic β-coronavirus (3). The SARS-CoV-2 genome, first published on January 24, 2020 (4), shares a nucleotide identity of 82% with SARS-CoV (5). Studies have confirmed that SARS-CoV-2 and SARS-CoV bind to the same host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), via their structural spike glycoprotein (S protein) (6). Host transmembrane serine protease 2 (TMPRSS2), along with ACE2 and virus S protein, is responsible for virus fusion and entry, and the three have been studied as potential targets for screening therapeutic compounds and repurposing drugs (7,8). In addition, many agents have been studied and identified based on virus-specific nucleic acids or proteins such as RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease 3Clpro (also termed Mpro), and papain-like proteases (PLpro), which play an important role in virus replication

COVID-19: Compreendendo a “tempestade de citocinas”

“…Desse modo, os vírions ficam aptos a infectar novas células. Vale ressaltar que cada vírus pode originar entre 10 mil e 100 mil cópias (Dong et al, 2020;Hu et al, 2020;Kumar et al, 2020;Lu et al, 2020).…”

Drug discovery to treat COVID-19 two years after its outbreak

“…The RdRp inhibitor remdesivir and the protease inhibitor lopinavir attracted considerable attention in early 2020 (41)(42)(43). A number of clinical studies have been conducted to test the efficacy and safety of these agents worldwide since the outbreak of the disease, and those studies have yielded evidence both corroborating and refuting their use to treat COVID-19 (41).…”

Effects of hydroxychloroquine and favipiravir on clinical course in outpatients with COVID-19

“…The disease is characterized by flu-like symptoms. Some patients are asymptomatic, pulmonary involvement often develop in symptomatic patients and progressive disease can be life threatening 1 .…”

“…Since the beginning of the pandemic, many drugs such as favipiravir, remdesivir, hydroxychloroquine, lopinavir / ritonavir have been used in the treatment of the disease. Chloroquine is 1 World Health Organisation (2020). Novel coronavirus-2019.…”

“…Favipiravir prevents the replication of the RNA virus by selectively inhibiting RNA-dependent RNA polymerase. Since the RNA-dependent RNA polymerase gene of SARS-CoV-2 is similar to influenza viruses, it has also been proposed in the treatment of COVID-19 [ 1 ]. Hydroxychloroquine and favipiravir have been used alone or in combination in the treatment of COVID-19 since the beginning of the pandemic in Turkey.…”