3 ms·

> The medication interrupts viral replication by preventing HIV from reaching the nucleus of an infected cell. How does it actually do it?

mrtesthah 2y ago
by preventing viral capsid assembly, as noted in the article. Once bound to the P24 capsid protein, the drug also interferes with other stages of the virus’ lifecycle[1]: >Lenacapavir is a multistage, selective inhibitor of HIV-1 capsid function that directly binds to the interface between capsid protein (p24) subunits in hexamers. Surface plasmon resonance sensorgrams showed dose-dependent and saturable binding of lenacapavir to cross-linked wild-type capsid hexamer with an equilibrium binding constant (KD) of 1.4 nM. Lenacapavir inhibits HIV-1 replication by interfering with multiple essential steps of the viral lifecycle, including capsid-mediated nuclear uptake of HIV-1 proviral DNA (by blocking nuclear import proteins binding to capsid), virus assembly and release (by interfering with Gag/Gag-Pol functioning, reducing production of capsid protein subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to malformed capsids). 1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e5652804-29c4-40d7-aeb2-0142ed2a7b5b#S12.4 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e56...
- deleted 2y ago
  [deleted]
tjohns 2y ago
From Wikipedia: "Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, production of capsid protein subunits, and capsid core formation[1]... It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell. This bond stabilizes the capsid structure and inhibits the functional disassembly of the capsid in infected cells.[2]" In other words, it prevents the virus' protein shell (capsid) from being built properly, which in turn prevents the virus from properly opening ("uncoating") once it enters a host cell. [1]: https://en.wikipedia.org/wiki/Lenacapavir https://en.wikipedia.org/wiki/Lenacapavir [2]: https://en.wikipedia.org/wiki/HIV_capsid_inhibition https://en.wikipedia.org/wiki/HIV_capsid_inhibition
- nothrowaways 2y ago
  Thought Lenacapavir was just a chemical. If it knows where the nucleus is, is Lenacapavir an organism?
  - tjohns 2y ago
    Yes, Lenacapavir is just a chemical. It's HIV itself that "knows" where the nucleus is and is actively trying to get there once it's inside your cell. It does this by walking itself along your cell's microtubial network. It would be fascinating if it wasn't so deadly. I'd recommend watching this video: https://vimeo.com/260291607 https://vimeo.com/260291607 See timestamps 1:33 and 2:47.
- akira2501 2y ago
  > It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell That's entirely cool to me, it operates by exploiting an "incidental construction feature" of the capsid and not targeting any specific feature in and of itself?

mrtesthah 2y ago

by preventing viral capsid assembly, as noted in the article. Once bound to the P24 capsid protein, the drug also interferes with other stages of the virus’ lifecycle[1]: >Lenacapavir is a multistage, selective inhibitor of HIV-1 capsid function that directly binds to the interface between capsid protein (p24) subunits in hexamers. Surface plasmon resonance sensorgrams showed dose-dependent and saturable binding of lenacapavir to cross-linked wild-type capsid hexamer with an equilibrium binding constant (KD) of 1.4 nM. Lenacapavir inhibits HIV-1 replication by interfering with multiple essential steps of the viral lifecycle, including capsid-mediated nuclear uptake of HIV-1 proviral DNA (by blocking nuclear import proteins binding to capsid), virus assembly and release (by interfering with Gag/Gag-Pol functioning, reducing production of capsid protein subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to malformed capsids). 1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e5652804-29c4-40d7-aeb2-0142ed2a7b5b#S12.4 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e56...

deleted 2y ago
[deleted]

tjohns 2y ago

From Wikipedia: "Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, production of capsid protein subunits, and capsid core formation[1]... It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell. This bond stabilizes the capsid structure and inhibits the functional disassembly of the capsid in infected cells.[2]" In other words, it prevents the virus' protein shell (capsid) from being built properly, which in turn prevents the virus from properly opening ("uncoating") once it enters a host cell. [1]: https://en.wikipedia.org/wiki/Lenacapavir https://en.wikipedia.org/wiki/Lenacapavir [2]: https://en.wikipedia.org/wiki/HIV_capsid_inhibition https://en.wikipedia.org/wiki/HIV_capsid_inhibition

nothrowaways 2y ago
Thought Lenacapavir was just a chemical. If it knows where the nucleus is, is Lenacapavir an organism?
- tjohns 2y ago
  Yes, Lenacapavir is just a chemical. It's HIV itself that "knows" where the nucleus is and is actively trying to get there once it's inside your cell. It does this by walking itself along your cell's microtubial network. It would be fascinating if it wasn't so deadly. I'd recommend watching this video: https://vimeo.com/260291607 https://vimeo.com/260291607 See timestamps 1:33 and 2:47.
akira2501 2y ago
> It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell That's entirely cool to me, it operates by exploiting an "incidental construction feature" of the capsid and not targeting any specific feature in and of itself?