Structural basis of SARS-CoV-2 polymerase inhibition by Favipiravir

AbstractThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogues, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs against the newly emerging viral diseases. Recent clinical trials of these two drugs for SARS-CoV-2 treatment revealed antiviral efficacies as well as side effects with different extents1–4. As a pyrazine derivative, Favipiravir could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides, which may further lead to mutations in progeny RNA copies due to the non-conserved base-pairing capacity5. Here, we determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues which may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed lights on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.

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Compelling Evidence for the Activity of Antiviral Peptides against SARS-CoV-2

Viruses ◽

10.3390/v13050912 ◽

2021 ◽

Vol 13 (5) ◽

pp. 912

Author(s):

Miray Tonk ◽

Daniel Růžek ◽

Andreas Vilcinskas

Keyword(s):

Ebola Virus ◽

High Specificity ◽

Antiviral Drugs ◽

Viral Diseases ◽

Therapeutic Peptides ◽

Evolution Of Resistance ◽

Antiviral Activities ◽

Virus Zika ◽

Emerging Viral Diseases ◽

Eukaryotic Organisms

Multiple outbreaks of epidemic and pandemic viral diseases have occurred in the last 20 years, including those caused by Ebola virus, Zika virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence or re-emergence of such diseases has revealed the deficiency in our pipeline for the discovery and development of antiviral drugs. One promising solution is the extensive library of antimicrobial peptides (AMPs) produced by all eukaryotic organisms. AMPs are widely known for their activity against bacteria, but many possess additional antifungal, antiparasitic, insecticidal, anticancer, or antiviral activities. AMPs could therefore be suitable as leads for the development of new peptide-based antiviral drugs. Sixty therapeutic peptides had been approved by the end of 2018, with at least another 150 in preclinical or clinical development. Peptides undergoing clinical trials include analogs, mimetics, and natural AMPs. The advantages of AMPs include novel mechanisms of action that hinder the evolution of resistance, low molecular weight, low toxicity toward human cells but high specificity and efficacy, the latter enhanced by the optimization of AMP sequences. In this opinion article, we summarize the evidence supporting the efficacy of antiviral AMPs and discuss their potential to treat emerging viral diseases including COVID-19.

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Nucleosides and Nucleoside Analogues as Emerging Antiviral Drugs

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x17999200820163234 ◽

2020 ◽

Vol 17 ◽

Author(s):

Mohamed Ibrahim Elzagheid

Keyword(s):

Significant Role ◽

Mode Of Action ◽

Crucial Role ◽

Viral Infections ◽

Antiviral Drugs ◽

Review Article ◽

Nucleoside Analogues ◽

The Past ◽

Nucleoside Drugs

: Nucleosides and their analogues have been in use for many years and have become essential for treating patients with viral infections. Many additional nucleoside drugs have been approved over the past decades. This strongly demonstrates how important these compounds are and the crucial role they play. Given that a significant amount of research and literature has been documented regarding nucleoside analogues, this review article mainly focuses the discussion on nucleosides and nucleoside analogous that have proven to play significant role or be emerging in the treatment of known viral infections. This covers the names, structures, applications, toxicity, and mode of action of relevant nucleoside analogues.

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Ocular manifestations of emerging viral diseases

Eye ◽

10.1038/s41433-020-01376-y ◽

2021 ◽

Author(s):

Ashwin Venkatesh ◽

Ravi Patel ◽

Simran Goyal ◽

Timothy Rajaratnam ◽

Anant Sharma ◽

...

Keyword(s):

Public Health ◽

Infectious Diseases ◽

Influenza A ◽

Emerging Infectious Diseases ◽

Global Scale ◽

Viral Diseases ◽

Valley Fever ◽

Ocular Manifestations ◽

Influenza A H1n1 ◽

Emerging Viral Diseases

AbstractEmerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.

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Aptamer Applications in Emerging Viral Diseases

Pharmaceuticals ◽

10.3390/ph14070622 ◽

2021 ◽

Vol 14 (7) ◽

pp. 622

Author(s):

Arne Krüger ◽

Ana Paula de Jesus Santos ◽

Vanessa de Sá ◽

Henning Ulrich ◽

Carsten Wrenger

Keyword(s):

Virus Assembly ◽

Viral Diseases ◽

Tissue Penetration ◽

Rna Molecules ◽

Viral Particles ◽

Pharmacokinetic Properties ◽

Oligonucleotide Library ◽

In Vivo Diagnosis ◽

Emerging Viral Diseases

Aptamers are single-stranded DNA or RNA molecules which are submitted to a process denominated SELEX. SELEX uses reiterative screening of a random oligonucleotide library to identify high-affinity binders to a chosen target, which may be a peptide, protein, or entire cells or viral particles. Aptamers can rival antibodies in target recognition, and benefit from their non-proteic nature, ease of modification, increased stability, and pharmacokinetic properties. This turns them into ideal candidates for diagnostic as well as therapeutic applications. Here, we review the recent accomplishments in the development of aptamers targeting emerging viral diseases, with emphasis on recent findings of aptamers binding to coronaviruses. We focus on aptamer development for diagnosis, including biosensors, in addition to aptamer modifications for stabilization in body fluids and tissue penetration. Such aptamers are aimed at in vivo diagnosis and treatment, such as quantification of viral load and blocking host cell invasion, virus assembly, or replication, respectively. Although there are currently no in vivo applications of aptamers in combating viral diseases, such strategies are promising for therapy development in the future.

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Antimalarial drugs—are they beneficial in rheumatic and viral diseases?—considerations in COVID-19 pandemic

Clinical Rheumatology ◽

10.1007/s10067-021-05805-5 ◽

2021 ◽

Author(s):

Bogna Grygiel-Górniak

Keyword(s):

Connective Tissue ◽

Viral Infections ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Antiviral Drugs ◽

In Vivo Studies ◽

Viral Diseases ◽

Cardiac Complications

AbstractThe majority of the medical fraternity is continuously involved in finding new therapeutic schemes, including antimalarial medications (AMDs), which can be useful in combating the 2019-nCoV: coronavirus disease (COVID-19). For many decades, AMDs have been widely used in the treatment of malaria and various other anti-inflammatory diseases, particularly to treat autoimmune disorders of the connective tissue. The review comprises in vitro and in vivo studies, original studies, clinical trials, and consensus reports for the analysis, which were available in medical databases (e.g., PubMed). This manuscript summarizes the current knowledge about chloroquine (CQ)/hydroxychloroquine (HCQ) and shows the difference between their use, activity, recommendation, doses, and adverse effects on two groups of patients: those with rheumatic and viral diseases (including COVID-19). In the case of connective tissue disorders, AMDs are prescribed for a prolonged duration in small doses, and their effect is observed after few weeks, whereas in the case of viral infections, they are prescribed in larger doses for a short duration to achieve a quick saturation effect. In rheumatic diseases, AMDs are well tolerated, and their side effects are rare. However, in some viral diseases, the effect of AMDs is questionable or not so noticeable as suggested during the initial prognosis. They are mainly used as an additive therapy to antiviral drugs, but recent studies have shown that AMDs can diminish the efficacy of some antiviral drugs and may cause respiratory, kidney, liver, and cardiac complications.

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COVID-19 in comparison with other emerging viral diseases: risk of geographic spread via travel

Tropical Diseases Travel Medicine and Vaccines ◽

10.1186/s40794-020-00129-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

A. Wilder-Smith

Keyword(s):

Reproduction Number ◽

Emerging Infectious Diseases ◽

Case Fatality ◽

The Elderly ◽

Air Travel ◽

Viral Diseases ◽

Fatality Rate ◽

The Past ◽

Geographic Spread ◽

Emerging Viral Diseases

Abstract Purpose of review The COVID-19 pandemic poses a major global health threat. The rapid spread was facilitated by air travel although rigorous travel bans and lockdowns were able to slow down the spread. How does COVID-19 compare with other emerging viral diseases of the past two decades? Recent findings Viral outbreaks differ in many ways, such as the individuals most at risk e.g. pregnant women for Zika and the elderly for COVID-19, their vectors of transmission, their fatality rate, and their transmissibility often measured as basic reproduction number. The risk of geographic spread via air travel differs significantly between emerging infectious diseases. Summary COVID-19 is not associated with the highest case fatality rate compared with other emerging viral diseases such as SARS and Ebola, but the combination of a high reproduction number, superspreading events and a globally immunologically naïve population has led to the highest global number of deaths in the past 20 decade compared to any other pandemic.

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