Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses.
Flaviviruses have caused large epidemics and ongoing outbreaks for centuries. They are now distributed in every continent infecting up to millions of people annually and may emerge to cause future epidemics. Some of the viruses from this group cause severe illnesses ranging from hemorrhagic to neuro...
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ftdoajarticles:oai:doaj.org/article:838d1bd06bb640feba4fb8d5e5237fa6 2023-05-15T15:13:28+02:00 Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses. Thamil Vaani Komarasamy Nur Amelia Azreen Adnan William James Vinod Rmt Balasubramaniam 2022-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010291 https://doaj.org/article/838d1bd06bb640feba4fb8d5e5237fa6 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010291 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010291 https://doaj.org/article/838d1bd06bb640feba4fb8d5e5237fa6 PLoS Neglected Tropical Diseases, Vol 16, Iss 4, p e0010291 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010291 2022-12-31T03:02:50Z Flaviviruses have caused large epidemics and ongoing outbreaks for centuries. They are now distributed in every continent infecting up to millions of people annually and may emerge to cause future epidemics. Some of the viruses from this group cause severe illnesses ranging from hemorrhagic to neurological manifestations. Despite decades of research, there are currently no approved antiviral drugs against flaviviruses, urging for new strategies and antiviral targets. In recent years, integrated omics data-based drug repurposing paired with novel drug validation methodologies and appropriate animal models has substantially aided in the discovery of new antiviral medicines. Here, we aim to review the latest progress in the development of both new and repurposed (i) direct-acting antivirals; (ii) host-targeting antivirals; and (iii) multitarget antivirals against flaviviruses, which have been evaluated both in vitro and in vivo, with an emphasis on their targets and mechanisms. The search yielded 37 compounds that have been evaluated for their efficacy against flaviviruses in animal models; 20 of them are repurposed drugs, and the majority of them exhibit broad-spectrum antiviral activity. The review also highlighted the major limitations and challenges faced in the current in vitro and in vivo evaluations that hamper the development of successful antiviral drugs for flaviviruses. We provided an analysis of what can be learned from some of the approved antiviral drugs as well as drugs that failed clinical trials. Potent in vitro and in vivo antiviral efficacy alone does not warrant successful antiviral drugs; current gaps in studies need to be addressed to improve efficacy and safety in clinical trials. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 4 e0010291 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Thamil Vaani Komarasamy Nur Amelia Azreen Adnan William James Vinod Rmt Balasubramaniam Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Flaviviruses have caused large epidemics and ongoing outbreaks for centuries. They are now distributed in every continent infecting up to millions of people annually and may emerge to cause future epidemics. Some of the viruses from this group cause severe illnesses ranging from hemorrhagic to neurological manifestations. Despite decades of research, there are currently no approved antiviral drugs against flaviviruses, urging for new strategies and antiviral targets. In recent years, integrated omics data-based drug repurposing paired with novel drug validation methodologies and appropriate animal models has substantially aided in the discovery of new antiviral medicines. Here, we aim to review the latest progress in the development of both new and repurposed (i) direct-acting antivirals; (ii) host-targeting antivirals; and (iii) multitarget antivirals against flaviviruses, which have been evaluated both in vitro and in vivo, with an emphasis on their targets and mechanisms. The search yielded 37 compounds that have been evaluated for their efficacy against flaviviruses in animal models; 20 of them are repurposed drugs, and the majority of them exhibit broad-spectrum antiviral activity. The review also highlighted the major limitations and challenges faced in the current in vitro and in vivo evaluations that hamper the development of successful antiviral drugs for flaviviruses. We provided an analysis of what can be learned from some of the approved antiviral drugs as well as drugs that failed clinical trials. Potent in vitro and in vivo antiviral efficacy alone does not warrant successful antiviral drugs; current gaps in studies need to be addressed to improve efficacy and safety in clinical trials. |
format |
Article in Journal/Newspaper |
author |
Thamil Vaani Komarasamy Nur Amelia Azreen Adnan William James Vinod Rmt Balasubramaniam |
author_facet |
Thamil Vaani Komarasamy Nur Amelia Azreen Adnan William James Vinod Rmt Balasubramaniam |
author_sort |
Thamil Vaani Komarasamy |
title |
Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses. |
title_short |
Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses. |
title_full |
Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses. |
title_fullStr |
Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses. |
title_full_unstemmed |
Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses. |
title_sort |
finding a chink in the armor: update, limitations, and challenges toward successful antivirals against flaviviruses. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010291 https://doaj.org/article/838d1bd06bb640feba4fb8d5e5237fa6 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 4, p e0010291 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010291 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010291 https://doaj.org/article/838d1bd06bb640feba4fb8d5e5237fa6 |
op_doi |
https://doi.org/10.1371/journal.pntd.0010291 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
16 |
container_issue |
4 |
container_start_page |
e0010291 |
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1766344019012485120 |