scholarly journals Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers

2021 ◽  
Author(s):  
Amit Kumar ◽  
Elena E Giorgi ◽  
Joshua J Tu ◽  
David R Martinez ◽  
Joshua Eudailey ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Maternal Plasma ◽  
Pediatric Hiv ◽  
World Health ◽  
Autologous Plasma ◽  
Maternal Risk ◽  
Health Organization ◽  
Hiv 1

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (env) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p=0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy could drive the evolution of variants fit for vertical transmission.

scholarly journals Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers

2021 ◽  
Vol 17 (4) ◽  
pp. e1009478
Author(s):  
Amit Kumar ◽  
Elena E. Giorgi ◽  
Joshua J. Tu ◽  
David R. Martinez ◽  
Joshua Eudailey ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Maternal Plasma ◽  
Pediatric Hiv ◽  
World Health ◽  
Autologous Plasma ◽  
Maternal Risk ◽  
Health Organization ◽  
Hiv 1

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (env) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p = 0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy may potentially drive the evolution of variants fit for vertical transmission.

scholarly journals Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Diagnostic Techniques ◽  
International Standards ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

scholarly journals Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients

2021 ◽  
Author(s):  
Lu Lu ◽  
Bobo Mok ◽  
Linlei Chen ◽  
Jacky Chan ◽  
Owen Tsang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
World Health ◽  
Whole Genome Sequence ◽  
Live Virus ◽  
Significant Difference ◽  
Antibody Titers ◽  
Ancestral Virus ◽  
Health Organization

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike protein mutations which have been found to evade neutralizing antibodies elicited by COVID-19 vaccines. The susceptibility of Omicron variant by vaccine-induced neutralizing antibodies are urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolates. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both omicron isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.

scholarly journals Neutralizing Antibody Escape during HIV-1 Mother-to-Child Transmission Involves Conformational Masking of Distal Epitopes in Envelope

2012 ◽  
Vol 86 (18) ◽  
pp. 9566-9582 ◽  
Author(s):  
Leslie Goo ◽  
Caitlin Milligan ◽  
Cassandra A. Simonich ◽  
Ruth Nduati ◽  
Julie Overbaugh
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Maternal Plasma ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
New Host ◽  
Glycosylation Sites ◽  
Molecular Determinants ◽  
Mother To Child ◽  
Hiv 1

HIV-1 variants transmitted to infants are often resistant to maternal neutralizing antibodies (NAbs), suggesting that they have escaped maternal NAb pressure. To define the molecular basis of NAb escape that contributes to selection of transmitted variants, we analyzed 5 viruses from 2 mother-to-child transmission pairs, in which the infant virus, but not the maternal virus, was resistant to neutralization by maternal plasma near transmission. We generated chimeric viruses between maternal and infant envelope clones obtained near transmission and examined neutralization by maternal plasma. The molecular determinants of NAb escape were distinct, even when comparing two maternal variants to the transmitted infant virus within one pair, in which insertions in V4 of gp120 and substitutions in HR2 of gp41 conferred neutralization resistance. In another pair, deletions and substitutions in V1 to V3 conferred resistance, but neither V1/V2 nor V3 alone was sufficient. Although the sequence determinants of escape were distinct, all of them involved modifications of potential N-linked glycosylation sites. None of the regions that mediated escape were major linear targets of maternal NAbs because corresponding peptides failed to compete for neutralization. Instead, these regions disrupted multiple distal epitopes targeted by HIV-1-specific monoclonal antibodies, suggesting that escape from maternal NAbs occurred through conformational masking of distal epitopes. This strategy likely allows HIV-1 to utilize relatively limited changes in the envelope to preserve the ability to infect a new host while simultaneously evading multiple NAb specificities present in maternal plasma.

scholarly journals Low neutralizing antibody titers against the Mu variant of SARS-CoV-2 in BNT162b2 vaccinated individuals

2021 ◽  
Author(s):  
Diego Alejandro Alvarez-Diaz ◽  
Ana L Munoz ◽  
Pilar Tavera-Rodriguez ◽  
Maria T Herrera-Sepulveda ◽  
Hector A Ruiz-Moreno ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
World Health ◽  
The World ◽  
Need To Evaluate ◽  
Surveillance Programs ◽  
Antibody Titers ◽  
Epidemiological Impact ◽  
Health Organization

Background Global surveillance programs for the virus that causes COVID-19 are showing the emergence of variants with mutations in the Spike protein, including the Mu variant, recently declared as a Variant of Interest (VOI) by the World Health Organization. Because these types of variants can be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Objectives To evaluate the sensitivity of the Mu variant (B.1.621) to neutralizing antibodies induced by the BNT162b2 vaccine. Study design Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated. Microneutralization assays were performed by incubating 120 TCDI50 of each SARS-CoV-2 isolate with five 2-fold serial dilutions of sera from 14 BNT162b2 vaccinated volunteers. The MN50 titer was calculated by the Reed-Muench formula Results The three isolated variants were Mu, a Variant of Interest (VOI), Gamma, a variant of concern (VOC), and B.1.111 that lacks genetic markers associated with greater virulence. At the end of August, the Mu and Gamma variants were widely distributed in Colombia. Mu was predominant (49%), followed by Gamma (25%). In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162-2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. Conclusions This study shows the importance of continuing with surveillance programs of emerging variants as well as the need to evaluate the neutralizing antibody response induced by other vaccines circulating in the country against Mu and other variants with high epidemiological impact.

scholarly journals Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission are Neutralization Resistant to Paired Maternal Plasma

2017 ◽  
Author(s):  
Amit Kumar ◽  
Claire E. P. Smith ◽  
Elena E. Giorgi ◽  
Joshua Eudailey ◽  
David R. Martinez ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Maternal Plasma ◽  
Pediatric Hiv ◽  
Viral Population ◽  
Single Genome Amplification ◽  
Genome Amplification ◽  
Implementation Challenges ◽  
Amplification Method ◽  
Single Genome ◽  
Hiv 1

AbstractDespite extensive genetic diversity of HIV-1 in chronic infection, infant HIV-1 infection involves selective transmission of a single or few maternal virus variants. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env)-specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we isolated HIV-1envgenes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Moreover, infant T/F pseudoviruses were overall more neutralization resistant compared to maternal non-transmitted plasma variants (p=0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the spector that enhancement of this response at the end of pregnancy could further reduce infant HIV infection risk.Author SummaryMother to child transmission (MTCT) of HIV-1 can occur during pregnancy (in utero), at the time of delivery (peripartum) or by breastfeeding (postpartum). With the availability of anti-retroviral therapy (ART), rate of MTCT of HIV-1 have been significantly lowered. However, significant implementation challenges remains in resource-poor areas, making it difficult to eliminate pediatric HIV. An improved understanding of the viral population (escape variants from autologous neutralizing antibodies) that lead to infection of infants at time of transmission will help in designing immune interventions to reduce vertical HIV-1 transmission. Here, we selected 16 HIV-1-infected mother-infant pairs from WITS cohort (from pre anti-retroviral era), where infants became infected peripartum. HIV-1envgene sequences were obtained by the single genome amplification method. The sensitivity of these infant Env pseudoviruses against paired maternal plasma and a panel of broadly neutralizing monoclonal antibodies (bNAbs) was analyzed. We demonstrated that the infant T/F viruses were more resistant against maternal plasma than non-transmitted maternal variants, but sensitive to most (bNAbs). Signature sequence analysis of infant T/F and non-transmitted maternal variants revealed the potential importance of V3 and MPER region for resistance against to paired maternal plasma. These findings provide insights for the design of maternal immunization strategies to enhance neutralizing antibodies that target V3 region of autologous virus populations, which could work synergistically with maternal ARVs to further reduce the rate of peripartum HIV-1 transmission.

scholarly journals Determinants of HIV-1 Late Presentation in Patients Followed in Europe

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 835
Author(s):  
Mafalda N. S. Miranda ◽  
Marta Pingarilho ◽  
Victor Pimentel ◽  
Maria do Rosário O. Martins ◽  
Anne-Mieke Vandamme ◽  
...  
Keyword(s):  
Late Presentation ◽  
World Health ◽  
Prevention Measures ◽  
Demographic Information ◽  
Late Presenters ◽  
Major Threat ◽  
Immunodeficiency Virus ◽  
Mode Of Transmission ◽  
Health Organization ◽  
Hiv 1

To control the Human Immunodeficiency Virus (HIV) pandemic, the World Health Organization (WHO) set the 90-90-90 target to be reached by 2020. One major threat to those goals is late presentation, which is defined as an individual presenting a TCD4+ count lower than 350 cells/mm3 or an AIDS-defining event. The present study aims to identify determinants of late presentation in Europe based on the EuResist database with HIV-1 infected patients followed-up between 1981 and 2019. Our study includes clinical and socio-demographic information from 89851 HIV-1 infected patients. Statistical analysis was performed using RStudio and SPSS and a Bayesian network was constructed with the WEKA software to analyze the association between all variables. Among 89,851 HIV-1 infected patients included in the analysis, the median age was 33 (IQR: 27.0–41.0) years and 74.4% were males. Of those, 28,889 patients (50.4%) were late presenters. Older patients (>56), heterosexuals, patients originated from Africa and patients presenting with log VL >4.1 had a higher probability of being late presenters (p < 0.001). Bayesian networks indicated VL, mode of transmission, age and recentness of infection as variables that were directly associated with LP. This study highlights the major determinants associated with late presentation in Europe. This study helps to direct prevention measures for this population.

scholarly journals Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope

2015 ◽  
Vol 89 (16) ◽  
pp. 8130-8151 ◽  
Author(s):  
Katie M. Kilgore ◽  
Megan K. Murphy ◽  
Samantha L. Burton ◽  
Katherine S. Wetzel ◽  
S. Abigail Smith ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Nonhuman Primate ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Cd40 Ligand ◽  
Antibody Activity ◽  
Immunodeficiency Virus ◽  
Antibody Profile ◽  
Hiv 1

ABSTRACTAntibodies that can neutralize diverse viral strains are likely to be an important component of a protective human immunodeficiency virus type 1 (HIV-1) vaccine. To this end, preclinical simian immunodeficiency virus (SIV)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection. However, these trials often rely on a limited selection of SIV strains with extreme neutralization phenotypes to assess vaccine-elicited antibody activity. To mirror the viral panels used to assess HIV-1 antibody breadth, we created and characterized a novel panel of 14 genetically and phenotypically diverse SIVsm envelope (Env) glycoproteins. To assess the utility of this panel, we characterized the neutralizing activity elicited by four SIVmac239 envelope-expressing DNA/modified vaccinia virus Ankara vector- and protein-based vaccination regimens that included the immunomodulatory adjuvants granulocyte-macrophage colony-stimulating factor, Toll-like receptor (TLR) ligands, and CD40 ligand. The SIVsm Env panel exhibited a spectrum of neutralization sensitivity to SIV-infected plasma pools and monoclonal antibodies, allowing categorization into three tiers. Pooled sera from 91 rhesus macaques immunized in the four trials consistently neutralized only the highly sensitive tier 1a SIVsm Envs, regardless of the immunization regimen. The inability of vaccine-mediated antibodies to neutralize the moderately resistant tier 1b and tier 2 SIVsm Envs defined here suggests that those antibodies were directed toward epitopes that are not accessible on most SIVsm Envs. To achieve a broader and more effective neutralization profile in preclinical vaccine studies that is relevant to known features of HIV-1 neutralization, more emphasis should be placed on optimizing the Env immunogen, as the neutralization profile achieved by the addition of adjuvants does not appear to supersede the neutralizing antibody profile determined by the immunogen.IMPORTANCEMany in the HIV/AIDS vaccine field believe that the ability to elicit broadly neutralizing antibodies capable of blocking genetically diverse HIV-1 variants is a critical component of a protective vaccine. Various SIV-based nonhuman primate vaccine studies have investigated ways to improve antibody-mediated protection against a heterologous SIV challenge, including administering adjuvants that might stimulate a greater neutralization breadth. Using a novel SIV neutralization panel and samples from four rhesus macaque vaccine trials designed for cross comparison, we show that different regimens expressing the same SIV envelope immunogen consistently elicit antibodies that neutralize only the very sensitive tier 1a SIV variants. The results argue that the neutralizing antibody profile elicited by a vaccine is primarily determined by the envelope immunogen and is not substantially broadened by including adjuvants, resulting in the conclusion that the envelope immunogen itself should be the primary consideration in efforts to elicit antibodies with greater neutralization breadth.

scholarly journals A booster dose of an inactivated vaccine increases neutralizing antibodies and T cell responses against SARS-CoV-2

2021 ◽  
Author(s):  
Barbara M Schultz ◽  
Felipe Melo-Gonzalez ◽  
Luisa F Duarte ◽  
Nicolas MS Galvez ◽  
Gaspar A Pacheco ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Booster Dose ◽  
Vaccination Schedule ◽  
World Health ◽  
Inactivated Vaccine ◽  
Protective Capacity ◽  
Cell Responses ◽  
Health Organization ◽  
Chilean Population

Numerous vaccines have been generated to decrease the morbidity and mortality of COVID-19. CoronaVac® is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO) to prevent COVID-19 that has safety and immunogenicity profiles described in different clinical trials. We previously reported an increase in levels of neutralizing antibodies two- and four-weeks after administering two doses of CoronaVac® in a two-week interval (0-14 day) vaccination schedule, as compared to pre-immune sera in adults in the Chilean population that are participating in phase 3 clinical trial. Here we report the levels of antibodies directed against the Receptor Binding Domain of the SARS-CoV-2 spike protein comparing their neutralizing capacities and the cellular response at five months after the second dose and four weeks after a booster (third) dose in volunteers immunized with two doses of CoronaVac®in a four-week interval (0-28 day) vaccination schedule. We observed a decrease in the levels of anti-SARS-CoV-2 antibodies with neutralizing capacities five months after the second dose (GMU 39.0 95% confidence interval (CI)(32.4-47.0), which increased up to 12 times at four weeks after the booster dose (GMU 499.4, 95% CI=370.6-673.0). Equivalent results were observed in adults aged 18-59 years old and individuals ≥60 years old. In the case of cellular response, we observed that activation of specific CD4+ T cells increases in time and reaches its maximum at four weeks after the booster dose in both groups. Our results support the notion that a booster dose of the SARS-CoV-2 inactivated vaccine increases the levels of neutralizing antibodies and the specific cellular response in adults of both groups, which is likely to boost the protective capacity of these vaccines against COVID-19.

scholarly journals Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

2019 ◽  
Author(s):  
Petter I. Andersen ◽  
Klara Krpina ◽  
Aleksandr Ianevski ◽  
Nastassia Shtaida ◽  
Eunji Jo ◽  
...  
Keyword(s):  
Influenza A ◽  
Rift Valley Fever Virus ◽  
Antiviral Agents ◽  
Viral Disease ◽  
World Health ◽  
Valley Fever ◽  
The World ◽  
Health Organization ◽  
Hiv 1

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

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