Broad-Spectrum Antiviral Strategies and Nucleoside Analogues

Geraghty, Robert J.; Aliota, Matthew T.; Bonnac, Laurent

doi:10.3390/v13040667

Cited by 123 publications

(88 citation statements)

References 97 publications

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“…In conclusion, although several studies have been conducted thus far on the action of antiretrovirals as therapy or prophylaxis against COVID-19 [ 11 , 111 , 112 , 113 ], the current clinical and pre-clinical evidence on the use of this drug deserves further investigation in the SARS-CoV-2 field in well-designed trials.…”

Section: Discussionmentioning

confidence: 99%

Tenofovir, Another Inexpensive, Well-Known and Widely Available Old Drug Repurposed for SARS-COV-2 Infection

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide with different clinical manifestations. Age and comorbidities may explain severity in critical cases and people living with human immunodeficiency virus (HIV) might be at particularly high risk for severe progression. Nonetheless, current data, although sometimes contradictory, do not confirm higher morbidity, risk of more severe COVID-19 or higher mortality in HIV-infected people with complete access to antiretroviral therapy (ART). A possible protective role of ART has been hypothesized to explain these observations. Anti-viral drugs used to treat HIV infection have been repurposed for COVID-19 treatment; this is also based on previous studies on severe acute respiratory syndrome virus (SARS-CoV) and Middle East respiratory syndrome virus (MERS-CoV). Among them, lopinavir/ritonavir, an inhibitor of viral protease, was extensively used early in the pandemic but it was soon abandoned due to lack of effectiveness in clinical trials. However, remdesivir, a nucleotide analog that acts as reverse-transcriptase inhibitor, which was tested early during the pandemic because of its wide range of antiviral activity against several RNA viruses and its safety profile, is currently the only antiviral medication approved for COVID-19. Tenofovir, another nucleotide analog used extensively for HIV treatment and pre-exposure prophylaxis (PrEP), has also been hypothesized as effective in COVID-19. No data on tenofovir’s efficacy in coronavirus infections other than COVID-19 are currently available, although information relating to SARS-CoV-2 infection is starting to come out. Here, we review the currently available evidence on tenofovir’s efficacy against SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Tenofovir, Another Inexpensive, Well-Known and Widely Available Old Drug Repurposed for SARS-COV-2 Infection

et al. 2021

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“…While the main disadvantage of host-targeted antivirals is the higher risk for host toxicity, an advantage is that the host-targets/proteins can be studied before a new virus emerges. In addition, a host-targeted approach often offers a higher barrier to the appearance of viral drug resistance [ 254 ]. The development and approval of such new antivirals could be of great use for viral pandemic preparedness and complement vaccines.…”

Section: Perspectives In the Field Of Virus Host Interaction And Capsid Uncoatingmentioning

confidence: 99%

How Influenza Virus Uses Host Cell Pathways during Uncoating

Moreira

Yamauchi

Matthias

2021

Cells

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Influenza is a zoonotic respiratory disease of major public health interest due to its pandemic potential, and a threat to animals and the human population. The influenza A virus genome consists of eight single-stranded RNA segments sequestered within a protein capsid and a lipid bilayer envelope. During host cell entry, cellular cues contribute to viral conformational changes that promote critical events such as fusion with late endosomes, capsid uncoating and viral genome release into the cytosol. In this focused review, we concisely describe the virus infection cycle and highlight the recent findings of host cell pathways and cytosolic proteins that assist influenza uncoating during host cell entry.

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“…Given that nucleoside analogues can exhibit a broad-spectrum antiviral effect in lethal mutagenesis [123,124] by augmenting mutation rates towards error catastrophe [125], the trajectory and mutational patterns of the viral mutation have clear implication in unraveling such effects. Three nucleoside analogues, ribavirin, 5-azacytidine and 5-fluorouracil active against seasonal H3N2 (A/Panama/2007/1999(H3N2) and A/Wyoming/03/2003(H3N2)) and laboratory-adapted H1N1 (A/Puerto Rico/8/1934(H1N1) and A/WSN/33(H1N1)), promoted the increase of defective viral particles [126].…”

Section: Design-build-test-learn Cycle For H5n8mentioning

confidence: 99%

Peering Into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

Yeo

Gan

2021

Preprint

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2014 marked the first emergence of avian influenza A(H5N8) in Jeonbuk Province, South Korea, which then quickly spread worldwide. In the midst of the 2020-21 H5N8 outbreak, it spread to domestic poultry and wild waterfowl shorebirds, leading to the first human infection in Astrakhan Oblast, Russia. Despite being clinically asymptomatic and without direct human-to-human transmission, the World Health Organisation stressed the need for continued risk assessment given the nature of Influenza to reassort and generate novel strains. Given its promiscuity and spread to humans, the urgency to understand the mechanisms of possible species jumping to avert disastrous pandemics is increasing. Addressing the epidemiology of H5N8 and its mechanisms of species jumping and its implications, mutational and reassortment libraries can potentially be built, allowing them to be tested on various models complemented with deep-sequencing and automation. With the knowledge on mutational patterns, cellular pathways, drug resistance mechanisms and effects of host proteins can allow better preparedness against H5N8 and other influenza A viruses.

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Broad-Spectrum Antiviral Strategies and Nucleoside Analogues

Cited by 123 publications

References 97 publications

Tenofovir, Another Inexpensive, Well-Known and Widely Available Old Drug Repurposed for SARS-COV-2 Infection

Tenofovir, Another Inexpensive, Well-Known and Widely Available Old Drug Repurposed for SARS-COV-2 Infection

How Influenza Virus Uses Host Cell Pathways during Uncoating

Peering Into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

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