Biology subjects

Van Lint, C. M.

Publications and source records attributed to Van Lint, C. M..

2 recordsLinked to original sources

bioRxiv2026

Identification of the cellular transcription factor KLF16 as a novel repressive epigenetic repressor of HIV-1 transcription

Despite antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1) persists in latently-infected cells through epigenetic and transcriptional mechanisms. Latency-reversing agents have failed clinically, partly due to incomplete understanding of HIV-1 latency reversal. Here, using DNA-affinity capture and mass spectrometry on the HIV-1 5 long terminal repeat (5LTR) enhancer-core promoter, we identify KLF16 (Kruppel-like Factor 16) as a novel regulator of HIV-1 gene expression. KLF16 binds to the HIV-1 5LTR in vivo at Sp1 binding sites, and KLF16 depletion reactivates latent HIV-1 in T-lymphoid and monocytic cell models. Mechanistically, KLF16 represses HIV-1 transcription by competing with Sp1 for promoter binding and by recruiting the Sin3A/HDAC1 and HP1/Suv39H1 repressive epigenetic complexes. KLF16 is also upregulated in CD4+ T cells from ART-treated people with HIV-1 upon T-cell activation. Additionally, All-Trans retinoic acid (ATRA) reactivates latent HIV-1 in myeloid cells, partly by downregulating KLF16. These findings establish KLF16 as a novel transcriptional repressor of HIV-1, identifying it as a potential promising therapeutic target for cure strategies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/722432v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1611026org.highwire.dtl.DTLVardef@16b5eaforg.highwire.dtl.DTLVardef@153b11org.highwire.dtl.DTLVardef@1d90330_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Highly potent antiviral drug candidates targeting SARS-CoV-2 nsp3 and nsp5

Faced with the emergence of three epidemics linked to a virus from the coronaviridae family over the last 20 years (SARS-CoV in China in 2002, MERS-CoV in Arabia in 2012, and SARS- CoV-2 worldwide in 2019), the identification of new antiviral treatments is of major public health concern. As part of the development of new drugs, several molecular modeling tools such as docking, virtual screening and molecular dynamics were combined with databases to decipher potential inhibitors of coronavirus targets. We performed a structure-based design of antiviral drugs targeting SARS-CoV-2 non-structural proteins 3 and 5 (nsp3 and nsp5) based on a high-throughput virtual screening of the ZINC15 database tranches for ligand docking followed by click chemistry with a particular attention paid to relaxed structures mimicking potential in vivo interactions. Based on the above in silico approaches, we selected two small molecules with high affinity binding for nsp3 and nsp5 named Amb929 and Amb701, respectively. We then assessed the antiviral activity of both the Amb929 and Amb701 against SARS-CoV-2 infection taking into account their potential cytotoxicity. Although both compounds inhibited SARS-CoV-2 replication in vitro, Amb929 displayed the most efficient anti-SARS-CoV-2 activity. Among these two drugs, Amb929 was less cytotoxic compared to Amb701, demonstrating an optimal anti-SARS-CoV-2 response with a high selectivity index in cell culture and a high inhibition of SARS-CoV-2 replication compared to untreated condition on a model of human airway epithelium (HAE), paving the way for the development of drugs with very potent anti-coronavirus activity.

microbiology↗