---
title: "2-HSB: A Novel Small Molecule with Dual 'Shock-and-Kill' Activity Against Latent HIV"
id: "pubmed-42673471"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42673471"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42673471/"
doi: "10.1002/jmv.71131"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# 2-HSB: A Novel Small Molecule with Dual 'Shock-and-Kill' Activity Against Latent HIV
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42673471
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42673471/)
- **DOI:** [10.1002/jmv.71131](https://doi.org/10.1002%2Fjmv.71131)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Antiretroviral therapy (ART) improves outcomes for people living with HIV (PLWH) but does not eliminate **latent HIV reservoirs**, which block a cure. - The **"Shock and Kill"** strategy uses latency-reversing agents (LRAs) to reactivate dormant provirus and then remove infected cells; most LRAs so far mainly provide the "shock" component only. - The authors screened a small-molecule library and identified 2-hydrido-2,2'-spirobi(1,3,2-benzodioxaphosphole) (**2-HSB**) as a candidate that both **reactivates latent HIV-1** and selectively induces cytopathic effects in latently infected reservoir cell lines. - **2-HSB** exhibits dual-action within a single compound: latency reversal and preferential induction of cell death in reservoir cell-line models, effectively combining both "shock" and "kill" activities. - Mechanistic data in the report indicate the HIV-1 **tat** protein appears to contribute to the selectivity of 2-HSB's cytopathic effect. - Single-cell analyses showed the reactivation and cytopathic effects were largely independent under tested conditions, suggesting reactivation was not simply a downstream consequence of cell death and vice versa. - Importantly, **2-HSB** induced viral transcription in **ex vivo CD4+ T cells** obtained from ART-suppressed PLWH, demonstrating activity in primary cells outside of cell-line models. - The authors conclude 2-HSB is a dual-action candidate that warrants further mechanistic study and additional ex vivo validation in primary, reservoir-bearing cells. - Keywords emphasized in the source include **HIV latency**, **LRA**, **Shock and Kill**, **apoptosis**, **latent HIV reservoir**, and **tat**. - The published work appears in Journal of Medical Virology (2026) and includes multiple institutional affiliations; full experimental details beyond the abstract were not reported in the source provided.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Intensive Care Medicine, Institute of Science Tokyo, Tokyo, Japan. * 2 Department of High-risk Infectious Disease Control, Institute of Science Tokyo, Tokyo, Japan. * 3 Viral Biochemistry Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA. * 4 Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Japan. * 5 Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. * 6 Department of Molecular Virology, Institute of Science Tokyo, Tokyo, Japan. * 7 Center for Infectious Disease Education and Analysis (TCIDEA), Institute of Science Tokyo, Tokyo, Japan. * PMID: **42673471** * DOI: [ 10.1002/jmv.71131 ](https://doi.org/10.1002/jmv.71131) Item in Clipboard # Identification of a Novel Small Molecule Facilitating HIV Elimination by the "Shock-And-Kill" Approach Yuichiro Hara et al. J Med Virol. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID J Med Virol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Med+Virol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Med+Virol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) . 2026 Sep;98(9):e71131. doi: 10.1002/jmv.71131. ### Authors [Yuichiro Hara](https://pubmed.ncbi.nlm.nih.gov/?term=Hara+Y&cauthor_id=42673471)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-1 "Department of Intensive Care Medicine, Institute of Science Tokyo, Tokyo, Japan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-2 "Department of High-risk Infectious Disease Control, Institute of Science Tokyo, Tokyo, Japan."), [Haruki Kitamura](https://pubmed.ncbi.nlm.nih.gov/?term=Kitamura+H&cauthor_id=42673471)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-3 "Viral Biochemistry Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA."), [Kouki Matsuda](https://pubmed.ncbi.nlm.nih.gov/?term=Matsuda+K&cauthor_id=42673471)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-4 "Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Japan."), [Chieko Fujisaki](https://pubmed.ncbi.nlm.nih.gov/?term=Fujisaki+C&cauthor_id=42673471)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-5 "Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan."), [Sayaka Sukegawa](https://pubmed.ncbi.nlm.nih.gov/?term=Sukegawa+S&cauthor_id=42673471)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-6 "Department of Molecular Virology, Institute of Science Tokyo, Tokyo, Japan.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-7 "Center for Infectious Disease Education and Analysis \(TCIDEA\), Institute of Science Tokyo, Tokyo, Japan."), [Kosuke Tanimoto](https://pubmed.ncbi.nlm.nih.gov/?term=Tanimoto+K&cauthor_id=42673471)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-2 "Department of High-risk Infectious Disease Control, Institute of Science Tokyo, Tokyo, Japan."), [Kenji Maeda](https://pubmed.ncbi.nlm.nih.gov/?term=Maeda+K&cauthor_id=42673471)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-4 "Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Japan."), [Hiroaki Takeuchi](https://pubmed.ncbi.nlm.nih.gov/?term=Takeuchi+H&cauthor_id=42673471)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-2 "Department of High-risk Infectious Disease Control, Institute of Science Tokyo, Tokyo, Japan.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42673471/#short-view-affiliation-7 "Center for Infectious Disease Education and Analysis \(TCIDEA\), Institute of Science Tokyo, Tokyo, Japan.") ### Affiliations * 1 Department of Intensive Care Medicine, Institute of Science Tokyo, Tokyo, Japan. * 2 Department of High-risk Infectious Disease Control, Institute of Science Tokyo, Tokyo, Japan. * 3 Viral Biochemistry Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland, USA. * 4 Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Japan. * 5 Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. * 6 Department of Molecular Virology, Institute of Science Tokyo, Tokyo, Japan. * 7 Center for Infectious Disease Education and Analysis (TCIDEA), Institute of Science Tokyo, Tokyo, Japan. * PMID: **42673471** * DOI: [ 10.1002/jmv.71131 ](https://doi.org/10.1002/jmv.71131) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Antiretroviral therapy (ART) has markedly improved the prognosis of people living with HIV (PLWH); however, latent viral reservoirs remain a major barrier to a cure. The "Shock and Kill" strategy aims to reactivate latent provirus with latency-reversing agents (LRAs) and subsequently eliminate the infected cells, yet most LRAs characterized to date provide only the "shock" component. Through screening a small-molecule library, we identified 2-hydrido-2,2'-spirobi(1,3,2-benzodioxaphosphole) (2-HSB) as a novel candidate that both reactivates latent HIV provirus and selectively induces cytopathic effects in latently infected reservoir cell lines, thereby exhibiting a dual "Shock and Kill" activity within a single compound. Mechanistically, the HIV-1 tat protein appears to contribute to this selectivity. At the single-cell level, the two effects appeared largely independent, indicating that, under the conditions tested, reactivation was not a consequence of cell death and vice versa. Importantly, 2-HSB induced viral transcription in ex vivo CD4+ T cells from ART-suppressed PLWH. Together, these findings identify 2-HSB as a dual-action candidate that reactivates latent HIV-1 and preferentially induces cytopathic effects in reservoir cell-line models, while supporting further mechanistic and ex vivo validation in primary reservoir-bearing cells. **Keywords:** HIV latency; LRA; Shock and Kill; apoptosis; latent HIV reservoir; tat. © 2026 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## References 1. 1. H. Mitsuya, K. J. Weinhold, P. A. Furman, et al., “3'‐Azido‐3'‐deoxythymidine (Bw A509U): An Antiviral Agent That Inhibits the Infectivity and Cytopathic Effect of Human T‐Lymphotropic Virus Type Iii/Lymphadenopathy‐Associated Virus in Vitro,” Proceedings of the National Academy of Sciences of the United States of America 82, no. 20 (1985): 7096–7100, . 2. 1. Palmisano L. and Vella S., “A Brief History of Antiretroviral Therapy of HIV Infection: Success and Challenges,” Annali dell'Istituto Superiore di Sanità 471 (2011): 44–48, . 3. 1. G. Hütter, D. Nowak, M. Mossner, et al., “Long‐Term Control of HIV by CCR5 Delta32/Delta32 Stem‐Cell Transplantation,” New England Journal of Medicine 360, no. 7 (2009): 692–698, . 4. 1. M. Pinkevych, D. Cromer, M. Tolstrup, et al., “HIV Reactivation From Latency After Treatment Interruption Occurs on Average Every 5‐8 Days‐‐Implications for HIV Remission,” PLoS Pathogens 11, no. 7 (July 2015): e1005000, . 5. 1. M. P. Davenport, D. S. Khoury, D. Cromer, S. R. Lewin, A. D. Kelleher, and S. J. Kent, “Functional Cure of HIV: The Scale of the Challenge,” Nature Reviews Immunology 19, no. 1 (January 2019): 45–54, . Show all 51 references ## MeSH terms * Anti-HIV Agents* / isolation & purification Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Anti-HIV+Agents%2Fisolation+and+purification%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Anti-HIV+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * Anti-HIV Agents* / pharmacology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Anti-HIV+Agents%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Anti-HIV+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * CD4-Positive T-Lymphocytes / virology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22CD4-Positive+T-Lymphocytes%2Fvirology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=CD4-Positive+T-Lymphocytes) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * Cell Line Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * Cytopathogenic Effect, Viral / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cytopathogenic+Effect%2C+Viral%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cytopathogenic+Effect%2C+Viral) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * HIV Infections / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22HIV+Infections%2Fdrug+therapy%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * HIV Infections / virology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22HIV+Infections%2Fvirology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * HIV-1* / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22HIV-1%2Fdrug+effects%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=HIV-1) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * HIV-1* / physiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22HIV-1%2Fphysiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=HIV-1) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673471/) * Proviruses / d
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