AVI-219 for COVID-19
c19early.org
COVID-19 Treatment Clinical Evidence
COVID-19 involves the interplay of 400+ viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes 6,000+ studies for 210+ treatments—over 17 million hours of research.
Only three high-profit early treatments are approved in the US.
In reality, many treatments reduce risk,
with 25 low-cost treatments approved across 163 countries.
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Naso/
oropharyngeal treatment Effective Treatment directly to the primary source of initial infection. -
Healthy lifestyles Protective Exercise, sunlight, a healthy diet, and good sleep all reduce risk.
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Immune support Effective Vitamins A, C, D, and zinc show reduced risk, as with other viruses.
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Thermotherapy Effective Methods for increasing internal body temperature, enhancing immune system function.
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Systemic agents Effective Many systemic agents reduce risk, and may be required when infection progresses.
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High-profit systemic agents Conditional Effective, but with greater access and cost barriers.
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Monoclonal antibodies Limited Utility Effective but rarely used—high cost, variant dependence, IV/SC admin.
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Acetaminophen Harmful Increased risk of severe outcomes and mortality.
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Remdesivir Harmful Increased mortality with longer followup. Increased kidney and liver injury, cardiac disorders.
AVI-219 may be beneficial for
COVID-19 according to the study below.
COVID-19 involves the interplay of 400+ viral and host proteins and factors providing many therapeutic targets.
Scientists have proposed 11,000+ potential treatments.
c19early.org analyzes
210+ treatments.
We have not reviewed AVI-219 in detail.
, The Mac1 ADP-ribosylhydrolase is a therapeutic target for SARS-CoV-2, eLife, doi:10.7554/elife.103484
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a threat to public health. Current therapeutics remain limited to direct-acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral life cycle by suppressing host innate immune responses. Genetic inactivation of Mac1 abrogates viral replication in vivo by potentiating host innate immune responses. However, it is unknown whether this can be achieved by pharmacologic inhibition and can therefore be exploited therapeutically. Here, we report a potent and selective lead small molecule, AVI-4206, that is effective in an in vivo model of SARS-CoV-2 infection. Standard cellular models indicate that AVI-4206 has high target engagement and can weakly inhibit viral replication in a gamma interferon- and Mac1 catalytic activity-dependent manner. However, a stronger antiviral effect for AVI-4206 is observed in human airway organoids and peripheral blood monocyte-derived macrophages. In an animal model of severe SARS-CoV-2 infection, AVI-4206 reduces viral replication, potentiates innate immune responses, and leads to a survival benefit. Our results provide pharmacological proof of concept that Mac1 is a valid therapeutic target via a novel immune-restoring mechanism that could potentially synergize with existing therapies targeting distinct, essential aspects of the coronaviral life cycle. This approach could be more widely used to target other viral macrodomains to develop antiviral therapeutics beyond COVID-19.