Identification of clickable HIV-1 capsid-targeting probes for viral replication inhibition
Copyright © 2024 Elsevier Ltd. All rights reserved..
Of the targets for HIV-1 therapeutics, the capsid core is a relatively unexploited but alluring drug target due to its indispensable roles throughout virus replication. Because of this, we aimed to identify "clickable" covalent modifiers of the HIV-1 capsid protein (CA) for future functionalization. We screened a library of fluorosulfate compounds that can undergo sulfur(VI) fluoride exchange (SuFEx) reactions, and five compounds were identified as hits. These molecules were further characterized for antiviral effects. Several compounds impacted in vitro capsid assembly. One compound, BBS-103, covalently bound CA via a SuFEx reaction to Tyr145 and had antiviral activity in cell-based assays by perturbing virus production, but not uncoating. The covalent binding of compounds that target the HIV-1 capsid could aid in the future design of antiretroviral drugs or chemical probes that will help study aspects of HIV-1 replication.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
|---|---|
| Enthalten in: |
Cell chemical biology - 31(2024), 3 vom: 21. März, Seite 477-486.e7 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
McFadden, William M [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antiviral Agents |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 13.04.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.chembiol.2024.02.012 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370083148 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370083148 | ||
| 003 | DE-627 | ||
| 005 | 20240413232614.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240324s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.chembiol.2024.02.012 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1374.xml |
| 035 | |a (DE-627)NLM370083148 | ||
| 035 | |a (NLM)38518746 | ||
| 035 | |a (PII)S2451-9456(24)00086-2 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a McFadden, William M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of clickable HIV-1 capsid-targeting probes for viral replication inhibition |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 13.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Of the targets for HIV-1 therapeutics, the capsid core is a relatively unexploited but alluring drug target due to its indispensable roles throughout virus replication. Because of this, we aimed to identify "clickable" covalent modifiers of the HIV-1 capsid protein (CA) for future functionalization. We screened a library of fluorosulfate compounds that can undergo sulfur(VI) fluoride exchange (SuFEx) reactions, and five compounds were identified as hits. These molecules were further characterized for antiviral effects. Several compounds impacted in vitro capsid assembly. One compound, BBS-103, covalently bound CA via a SuFEx reaction to Tyr145 and had antiviral activity in cell-based assays by perturbing virus production, but not uncoating. The covalent binding of compounds that target the HIV-1 capsid could aid in the future design of antiretroviral drugs or chemical probes that will help study aspects of HIV-1 replication | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HIV-1 | |
| 650 | 4 | |a SuFEx | |
| 650 | 4 | |a antiviral screen | |
| 650 | 4 | |a capsid | |
| 650 | 4 | |a capsid-targeting compound | |
| 650 | 4 | |a click chemistry | |
| 650 | 7 | |a Capsid Proteins |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Casey-Moore, Mary C |e verfasserin |4 aut | |
| 700 | 1 | |a Bare, Grant A L |e verfasserin |4 aut | |
| 700 | 1 | |a Kirby, Karen A |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Gencheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Slack, Ryan L |e verfasserin |4 aut | |
| 700 | 1 | |a Snyder, Alexa A |e verfasserin |4 aut | |
| 700 | 1 | |a Lorson, Zachary C |e verfasserin |4 aut | |
| 700 | 1 | |a Kaufman, Isabella L |e verfasserin |4 aut | |
| 700 | 1 | |a Cilento, Maria E |e verfasserin |4 aut | |
| 700 | 1 | |a Tedbury, Philip R |e verfasserin |4 aut | |
| 700 | 1 | |a Gembicky, Milan |e verfasserin |4 aut | |
| 700 | 1 | |a Olson, Arthur J |e verfasserin |4 aut | |
| 700 | 1 | |a Torbett, Bruce E |e verfasserin |4 aut | |
| 700 | 1 | |a Sharpless, K Barry |e verfasserin |4 aut | |
| 700 | 1 | |a Sarafianos, Stefan G |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell chemical biology |d 2016 |g 31(2024), 3 vom: 21. März, Seite 477-486.e7 |w (DE-627)NLM257252177 |x 2451-9448 |7 nnns |
| 773 | 1 | 8 | |g volume:31 |g year:2024 |g number:3 |g day:21 |g month:03 |g pages:477-486.e7 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.chembiol.2024.02.012 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 31 |j 2024 |e 3 |b 21 |c 03 |h 477-486.e7 | ||