Few amino acid signatures distinguish HIV-1 subtype B pandemic and non-pandemic strains

Arantes, Ighor; Ribeiro-Alves, Marcelo; Azevedo, Suwellen Sardinha Dias de; Delatorre, Edson; Bello, Gonzalo

doi:10.1371/journal.pone.0238995

Cited by 2 publications

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References 69 publications

(109 reference statements)

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“…The challenges include laborious and time-consuming production techniques, high cost of production, instability of the developed antibody, delivery systems of the antibodies, and risk of treatment failure due to variation in immunological responses of antibodies therapy [ 22 ]. Moreover, the different clades have mutations in gp120 protein affecting the neutralization potential of these antibodies [ 23 ]. To overcome these challenges, small molecule mimetics of large biological molecules can be developed as therapeutic agents against HIV infection.…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry

et al. 2023

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Broadly neutralizing antibodies (bNAbs) are potent in neutralizing a wide range of HIV strains. VRC01 is a CD4-binding-site (CD4-bs) class of bNAbs that binds to the conserved CD4-binding region of HIV-1 envelope (env) protein. Natural products that mimic VRC01 bNAbs by interacting with the conserved CD4-binding regions may serve as a new generation of HIV-1 entry inhibitors by being broadly reactive and potently neutralizing. This study aimed to identify compounds that mimic VRC01 by interacting with the CD4-bs of HIV-1 gp120 and thereby inhibiting viral entry into target cells. Libraries of purchasable natural products were virtually screened against clade A/E recombinant 93TH057 (PDB: 3NGB) and clade B (PDB ID: 3J70) HIV-1 env protein. Protein–ligand interaction profiling from molecular docking and dynamics simulations showed that the compounds had intermolecular hydrogen and hydrophobic interactions with conserved amino acid residues on the CD4-binding site of recombinant clade A/E and clade B HIV-1 gp120. Four potential lead compounds, NP-005114, NP-008297, NP-007422, and NP-007382, were used for cell-based antiviral infectivity inhibition assay using clade B (HXB2) env pseudotype virus (PV). The four compounds inhibited the entry of HIV HXB2 pseudotype viruses into target cells at 50% inhibitory concentrations (IC50) of 15.2 µM (9.7 µg/mL), 10.1 µM (7.5 µg/mL), 16.2 µM (12.7 µg/mL), and 21.6 µM (12.9 µg/mL), respectively. The interaction of these compounds with critical residues of the CD4-binding site of more than one clade of HIV gp120 and inhibition of HIV-1 entry into the target cell demonstrate the possibility of a new class of HIV entry inhibitors.

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Section: Introductionmentioning

confidence: 99%

Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry

et al. 2023

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“…One of those viruses, however, migrated from the Caribbean to the United States around the late 1960s and established a pandemic clade, called B PAN , that was then disseminated worldwide ( Worobey et al, 2016 ). The remarkable dissemination of the B PAN clade was probably shaped by ecological, rather than virological factors ( Gilbert et al, 2007 ; Arantes et al, 2020 ); but there are no studies comparing the epidemic potential of B CAR and B PAN clades co-circulating outside the Caribbean region.…”

Section: Introductionmentioning

confidence: 99%

Dissemination Dynamics of HIV-1 Subtype B Pandemic and Non-pandemic Lineages Circulating in Amazonas, Brazil

et al. 2022

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The HIV-1 epidemic in the Amazonas state, as in most of Brazil, is dominated by subtype B. The state, nonetheless, is singular for its significant co-circulation of the variants BCAR, which can mostly be found in the Caribbean region, and BPAN, a clade that emerged in the United States and aggregates almost the totality of subtype B infections world-wide. The Amazonian HIV-1 epidemic provides a unique scenario to compare the epidemic potential of BPAN and BCAR clades spreading in the same population. To reconstruct the spatiotemporal dynamic and demographic history of both subtype B lineages circulating in Amazonas, we analyzed 1,272 HIV-1 pol sequences sampled in that state between 2009 and 2018. Our phylogeographic analyses revealed that while most BCAR infections resulted from a single successful founder event that took place in the Amazonas state around the late 1970s, most BPAN infections resulted from the expansion of multiple clusters seeded in the state since the late 1980s. Our data support the existence of at least four large clusters of the pandemic form in Amazonas, two of them nested in Brazil’s largest known subtype B cluster (BBR–I), and two others resulting from new introductions detected here. The reconstruction of the demographic history of the most prevalent BPAN (n = 4) and BCAR (n = 1) clades identified in Amazonas revealed that all clades displayed a continuous expansion [effective reproductive number (Re) > 1] until most recent times. During the period of co-circulation from the late 1990s onward, the Re of Amazonian BPAN and BCAR clusters behaved quite alike, fluctuating between 2.0 and 3.0. These findings support that the BCAR and BPAN variants circulating in the Brazilian state of Amazonas displayed different evolutionary histories, but similar epidemic trajectories and transmissibility over the last two decades, which is consistent with the notion that both subtype B variants display comparable epidemic potential. Our findings also revealed that despite significant advances in the treatment of HIV infections in the Amazonas state, BCAR and BPAN variants continue to expand and show no signs of the epidemic stabilization observed in other parts of the country.

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Few amino acid signatures distinguish HIV-1 subtype B pandemic and non-pandemic strains

Cited by 2 publications

References 69 publications

Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry

Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry

Dissemination Dynamics of HIV-1 Subtype B Pandemic and Non-pandemic Lineages Circulating in Amazonas, Brazil

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