Broad-spectrum coronavirus antiviral drug discovery
INTRODUCTION: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic.
| Errataetall: |
CommentIn: Travel Med Infect Dis. 2020 May - Jun;35:101577. - PMID 32044388 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Expert opinion on drug discovery - 14(2019), 4 vom: 15. Apr., Seite 397-412 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Totura, Allison L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.03.2020 Date Revised 07.12.2022 published: Print-Electronic CommentIn: Travel Med Infect Dis. 2020 May - Jun;35:101577. - PMID 32044388 Citation Status MEDLINE |
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| doi: |
10.1080/17460441.2019.1581171 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM294730281 |
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| 500 | |a CommentIn: Travel Med Infect Dis. 2020 May - Jun;35:101577. - PMID 32044388 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic | ||
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