Antivirals: Role & How They Act-Remdesivir & Covid-19 YouTube Lecture Handouts

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Antivirals: Role & How They Act - Remdesivir & Covid-19

Title: Anti-Virals – Role & How They Act Remdesivir

Anti-Virals
  • Unlike other antimicrobials, antiviral drugs do not deactivate or destroy the microbe (in this case, the virus) but act by inhibiting replication. In this way, they prevent the viral load from increasing to a point where it could cause pathogenesis, allowing the body՚s innate immune mechanisms to neutralize the virus.
  • Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID-19 pandemic, Remdesivir was approved or authorized for emergency use to treat COVID-19 in around 50 countries.
  • Updated guidelines from the World Health Organization in November 2020 include a conditional recommendation against the use of Remdesivir for the treatment of COVID-19. Remdesivir was originally developed to treat hepatitis C, and was subsequently investigated for Ebola virus disease and Marburg virus infections before being studied as a post-infection treatment for COVID-19

How Virus Acts?

  • Attachment to a host cell. (HIV Drugs – CCR5 antogonists)
  • Viral Entry (endocytosis, fusion) - Enfurvirtide
  • Release of viral genes and possibly enzymes into the host cell (uncoding) – Amantadine, rimantadine
  • Replication of viral components using host-cell machinery. – Zidovudine, Lamivudine, Nevirapine
  • Assembly of viral components into complete viral particles - Fomivirsen
  • Release of viral particles to infect new host cells – Oseltamivir, Zanamivir

Viruses consist of a genome and sometimes a few enzymes stored in a capsule made of protein (called a capsid) , and sometimes covered with a lipid layer (sometimes called an β€˜envelope’ ) . Viruses cannot reproduce on their own and instead propagate by subjugating a host cell to produce copies of themselves, thus producing the next generation.

How Anti-Virals Act

  • Inhibit viral attachment
  • Prevent genetic copying of virus
  • Prevent viral protein production, vital for reproduction of virus.

Anti-Virals Types

Anti-Virals Types
  • First experimental antivirals were developed in the 1960s, mostly to deal with herpes viruses, and were found using traditional trial-and-error drug discovery methods.
  • Only in the 1980s, when the full genetic sequences of viruses began to be unraveled, did researchers begin to learn how viruses worked in detail, and exactly what chemicals were needed to thwart their reproductive cycle.
  • Few drugs are selective enough to prevent viral replication without injury to the infected host cells
  • Candidates for antivirals are individuals who have a higher risk for complications from influenza: adults 65 or older; people with chronic diseases such as heart, lung, or kidney disease; children under age 4; or anyone with a compromised immune system.
  • Remdesivir (Veklury) was the first drug approved by the FDA for treating the SARS-CoV-2 virus. It is indicated for treatment of COVID-19 disease in hospitalized adults and children aged 12 years and older who weigh at least 40 kg. The broad-spectrum antiviral is a nucleotide analog prodrug. Remdesivir is a nucleotide analogue with a proved mechanism of action as an inhibitor of RNA-dependent RNA polymerases. This mechanism is probably involved in an antiviral activity against SARS-CoV-2.

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