3-Hydroxyphthalic Anhydride-Modified Chicken Ovalbumin Exhibits Potent and Broad Anti-HIV-1 Activity: a Potential Microbicide for Preventing Sexual Transmission of HIV-1

Li, Lin; He, Lili; Tan, Suiyi; Guo, Xinhua; Liang, Hong; Qi, Zhi; Pan, Chungen; An, Xiuli; Jiang, Shibo; Liu, Shuwen

doi:10.1128/aac.01046-09

Cited by 36 publications

(70 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, we demonstrated that the percentage of anhydride-modified residues was proportional to the entry-inhibitory activity of anhydride-modified proteins (23,25). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…As shown in Table 2, the EC 50 of HP-HSA showed no significant change when it was mixed with serum from different species from that when it was mixed with Dulbecco modified Eagle medium (DMEM), while the EC 90 values increased slightly, but it still inhibited Zaire PsV entry by 90% at the micromolar scale. Our previous studies demonstrated that anhydride-modified proteins could be utilized as anti-HIV or anti-HPV microbicides (25,26,28). In order to determine whether HP-HSA could be developed as an anti-EBOV microbicide against the sexual transmission of EBOV, we tested the antiviral activity of HP-HSA against both Zaire PsV and Sudan PsV entry in human genital fluids, including seminal fluid (SF) and vaginal fluid simulant (VFS).…”

Section: Resultsmentioning

confidence: 99%

“…Anhydride-modified proteins have been identified to be inhibitors of the entry of many enveloped or nonenveloped viruses (23)(24)(25)27). To investigate the inhibitory effects of anhydride-modified proteins on the entry of EBOV pseudovirus (PsV), we constructed a small library of anhydride-modified proteins, including 3-hydroxyphthalic anhydride (HP)-modified human serum albumin (HSA) (HP-HSA), HP-modified ␤-lactoglobulin (␤-LG) (HP-␤-LG), HP-modified chicken ovalbumin (OVA) (HP-OVA), HP-modified bovine serum albumin (BSA) (HP-BSA), maleic anhydride (ML)-modified HSA (ML-HSA), ML-modified ␤-LG (ML-␤-LG), succinic anhydride (SU)-modified HSA (SU-HSA), and SU-modified ␤-LG (SU-␤-LG).…”

Section: Resultsmentioning

confidence: 99%

“…In our previous studies, we have demonstrated that several kinds of viruses, including human immunodeficiency virus (HIV), human papillomavirus (HPV), and respiratory syncytial virus (RSV), can be inhibited at the viral entry step by anhydride-modified proteins (23)(24)(25). Furthermore, one kind of anhydride-modified bovine protein, ␤-lactoglobulin (␤-LG), was clinically applied to treat HPV infection (26).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Chemically Modified Human Serum Albumin Potently Blocks Entry of Ebola Pseudoviruses and Viruslike Particles

Xia

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Ebola virus (EBOV), the causative pathogen of the deadly Ebola virus disease (EVD), can be transmitted via contact with EVD patients, including sexual contact with EVD survivors. At present, no licensed vaccine or therapeutic is available. In this study, we compared eight anhydride-modified proteins for their entry-inhibitory activity against the pseudovirus (PsV) carrying the envelope glycoprotein (GP) of the EBOV Zaire or Sudan species (Zaire PsV and Sudan PsV, respectively). We found that 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) was the most effective in inhibiting the entry of both Zaire PsV and Sudan PsV, with the 50% effective concentration being at the nanomolar level and with HP-HSA being more potent than EBOV-neutralizing antibody MIL77-2 (4G7, a component antibody of the ZMapp drug cocktail). The combination of HP-HSA and MIL77-2 exhibited a synergistic effect. HP-HSA had no obvious in vitro or in vivo toxicity. The EBOV PsV entryinhibitory activity of HP-HSA remained intact after storage at 45°C for 8 weeks, suggesting that HP-HSA has the potential for worldwide use, including tropical regions in African countries, as either a therapeutic to treat EBOV infection or a prophylactic microbicide to prevent the sexual transmission of EBOV.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Chemically Modified Human Serum Albumin Potently Blocks Entry of Ebola Pseudoviruses and Viruslike Particles

Xia

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the fourth day postinfection, 100 l of culture supernatants were collected from each well, mixed with equal volumes of 5% Triton X-100, and assayed for p24 antigen by ELISA. The inhibition of P20 and its variants on infection by the HIV-1 R5 strain Bal, the primary HIV-1 isolates, and the VSV-G pseudovirus was determined as described before (31). Briefly, 100 l of TZM-bl cells (1 ϫ 10 5 /ml) was precultured overnight and infected with a virus at 100 TCID 50 in the presence or absence of the test peptide overnight.…”

mentioning

confidence: 99%

Identification of a gp41 Core-Binding Molecule with Homologous Sequence of Human TNNI3K-Like Protein as a Novel Human Immunodeficiency Virus Type 1 Entry Inhibitor

Zhu

et al. 2010

J Virol

Self Cite

View full text Add to dashboard Cite

Human immunodeficiency virus type 1 (HIV-1) gp41 plays a critical role in the viral fusion process, and its N-and C-terminal heptad repeat domains serve as important targets for developing anti-HIV-1 drugs, like T-20 (generic name, enfuvirtide; brand name, Fuzeon). Here, we conducted a yeast two-hybrid screening on a human bone marrow cDNA library using the recombinant soluble gp41 ectodomain as the bait and identified a novel gp41 core-binding molecule, designated P20. P20 showed no homology with a current HIV fusion inhibitor, T-20, but had sequence homology to a human protein, troponin I type 3 interacting kinase (TNNI3K)-like protein. While it could bind to the six-helix bundle core structure formed by the N-and C-terminal heptad repeats, P20 did not interrupt the formation of the six-helix bundle. P20 was effective in blocking HIV-1 Env-mediated syncytium formation and inhibiting infection by a broad spectrum of HIV-1 strains with distinct subtypes and coreceptor tropism, while it was ineffective against other enveloped viruses, such as vesicular stomatitis virus and influenza A virus. P20 exhibited no significant cytotoxicity to the CD4 ؉ cells that were used for testing antiviral activity. Among the 11 P20 mutants, four analogous peptides with a common motif (WGRLEGRRT) exhibited significantly reduced anti-HIV-1 activity, suggesting that this region is the critical active site of P20. Therefore, this peptide can be used as a lead for developing novel HIV fusion inhibitors and as a probe for studying the membranefusogenic mechanism of HIV.

show abstract

Trilobatin as an HIV‐1 entry inhibitor targeting the HIV‐1 Gp41 envelope

et al. 2018

Self Cite

View full text Add to dashboard Cite

HIV-1 transmembrane protein gp41 plays a crucial role by forming a stable six-helix bundle during HIV entry. Due to highly conserved sequence of gp41, the development of an effective and safe small-molecule compound targeting gp41 is a good choice. Currently, natural polyanionic ingredients with anti-HIV activities have aroused concern. Here, we first discovered that a glycosylated dihydrochalcone, trilobatin, exhibited broad anti-HIV-1 activity and low cytotoxicity in vitro. Site-directed mutagenesis analysis suggested that the hydrophobic residue (I564) located in gp41 pocket-forming site is pivotal for anti-HIV activity of trilobatin. Furthermore, trilobatin displayed synergistic anti-HIV activities combined with other antiretroviral agents. Trilobatin has a good potential to be developed as a small-molecule HIV-1 entry inhibitor for clinical combination therapy.

show abstract

3-Hydroxyphthalic Anhydride-Modified Chicken Ovalbumin Exhibits Potent and Broad Anti-HIV-1 Activity: a Potential Microbicide for Preventing Sexual Transmission of HIV-1

Cited by 36 publications

References 73 publications

Chemically Modified Human Serum Albumin Potently Blocks Entry of Ebola Pseudoviruses and Viruslike Particles

Chemically Modified Human Serum Albumin Potently Blocks Entry of Ebola Pseudoviruses and Viruslike Particles

Identification of a gp41 Core-Binding Molecule with Homologous Sequence of Human TNNI3K-Like Protein as a Novel Human Immunodeficiency Virus Type 1 Entry Inhibitor

Trilobatin as an HIV‐1 entry inhibitor targeting the HIV‐1 Gp41 envelope

Contact Info

Product

Resources

About