scholarly journals Ivermectin: An Anti-Parasitic Drug that has Potential for Repurposing for COVID-19

BioMedica ◽  
2020 ◽  
Vol 36 (2S) ◽  
pp. 31-32
Author(s):  
Maryam Rashid ◽  
Mariyam Iftikhar Piracha
Keyword(s):  
Human Immunodeficiency Virus ◽  
Global Health ◽  
Antiviral Activity ◽  
Dengue Virus ◽  
Broad Spectrum ◽  
Macrocyclic Lactone ◽  
Antiviral Drug ◽  
Viral Rna ◽  
Deep Impact ◽  
Immunodeficiency Virus

<p>After global health catastrophe due to Coronavirus disease-2019 (COVID-19), a deep impact on the way we perceive our world and our everyday lives has been imprinted. Till now, no specific antiviral drug has been proven effective for curing patients. Ivermectin, the broad-spectrum macrocyclic lactone has proven to exert antiviral activity against human immunodeficiency virus (HIV), dengue virus and now capability to reduce viral RNA up to 5,000-fold after 48 h of infection with SARS-CoV-2.</p>

scholarly journals Restoration of the antiviral activity of 3′-azido-3′-deoxythymidine (AZT) against AZT-resistant human immunodeficiency virus by delivery of engineered thymidylate kinase to T cells

2008 ◽  
Vol 89 (7) ◽  
pp. 1672-1679 ◽  
Author(s):  
Arnon Lavie ◽  
Ying Su ◽  
Mahmood Ghassemi ◽  
Richard M. Novak ◽  
Michael Caffrey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
T Cells ◽  
Antiviral Activity ◽  
Nucleoside Analogue ◽  
Combined Treatment ◽  
Antiviral Drug ◽  
Thymidylate Kinase ◽  
Highly Active ◽  
Immunodeficiency Virus

Emergence of antiviral drug resistance is a major challenge to human immunodeficiency virus (HIV) therapy. The archetypal example of this problem is loss of antiviral activity of the nucleoside analogue 3′-azido-3′-deoxythymidine (AZT), caused by mutations in reverse transcriptase (RT), the viral polymerase. AZT resistance results from an imbalance between rates of AZT-induced proviral DNA chain termination and RT-induced excision of the chain-terminating nucleotide. Conversion of the AZT prodrug from its monophosphorylated to diphosphorylated form by human thymidylate kinase (TMPK) is inefficient, resulting in accumulation of the monophosphorylated AZT metabolite (AZT-MP) and a low concentration of the active triphosphorylated metabolite (AZT-TP). We reasoned that introduction of an engineered, highly active TMPK into T cells would overcome this functional bottleneck in AZT activation and thereby shift the balance of AZT activity sufficiently to block replication of formerly AZT-resistant HIV. Molecular engineering was used to link highly active, engineered TMPKs to the protein transduction domain of Tat for direct cell delivery. Combined treatment of HIV-infected T cells with AZT and these cell-permeable, engineered TMPKs restored AZT-induced repression of viral production. These results provide an experimental basis for the development of new strategies to therapeutically increase the intracellular concentrations of active nucleoside analogue metabolites as a means to overcome emerging drug resistance.

scholarly journals Newly Designed Six-Membered Azasugar Nucleotide-Containing Phosphorothioate Oligonucleotides as Potent Human Immunodeficiency Virus Type 1 Inhibitors

2005 ◽  
Vol 49 (10) ◽  
pp. 4110-4120 ◽  
Author(s):  
Dong-Seong Lee ◽  
Kyeong-Eun Jung ◽  
Cheol-Hee Yoon ◽  
Hong Lim ◽  
Yong-Soo Bae
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Broad Spectrum ◽  
Mononuclear Cells ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT A series of modified oligonucleotides (ONs), characterized by a phosphorothioate (P═S) backbone and a six-membered azasugar (6-AZS) as a sugar substitute in a nucleotide, were newly synthesized and assessed for their ability to inhibit human immunodeficiency virus type 1 (HIV-1) via simple treatment of HIV-1-infected cultures, without any transfection process. While unmodified P═S ONs exhibited only minor anti-HIV-1 activity, the six-membered azasugar nucleotide (6-AZN)-containing P═S oligonucleotides (AZPSONs) exhibited remarkable antiviral activity against HIV-1/simian-human immunodeficiency virus (SHIV) replication and syncytium formation (50% effective concentration = 0.02 to 0.2 μM). The AZPSONs exhibited little cytotoxicity at concentrations of up to 100 μM. DBM 2198, one of the most effective AZPSONs, exhibited antiviral activity against a broad spectrum of HIV-1, including T-cell-tropic, monotropic, and even drug-resistant HIV-1 variants. The anti-HIV-1 activities of DBM 2198 were similarly maintained in HIV-1-infected cultures of peripheral blood mononuclear cells. When we treated severely infected cultures with DBM 2198, syncytia disappeared completely within 2 days. Taken together, our results indicate that DBM 2198 and other AZPSONs may prove useful in the further development of safe and effective AIDS-therapeutic drugs against a broad spectrum of HIV-1 variants.

scholarly journals In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Novel Protease Inhibitor of Human Immunodeficiency Virus Type 1

2007 ◽  
Vol 51 (11) ◽  
pp. 4036-4043 ◽  
Author(s):  
Serge Dandache ◽  
Guy Sévigny ◽  
Jocelyn Yelle ◽  
Brent R. Stranix ◽  
Neil Parkin ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Highly Active Antiretroviral Therapy ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Resistance Profile ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Despite the success of highly active antiretroviral therapy, the current emergence and spread of drug-resistant variants of human immunodeficiency virus (HIV) stress the need for new inhibitors with distinct properties. We designed, produced, and screened a library of compounds based on an original l-lysine scaffold for their potentials as HIV type 1 (HIV-1) protease inhibitors (PI). One candidate compound, PL-100, emerged as a specific and noncytotoxic PI that exhibited potent inhibition of HIV-1 protease and viral replication in vitro (Ki , ∼36 pM, and 50% effective concentration [EC50], ∼16 nM, respectively). To confirm that PL-100 possessed a favorable resistance profile, we performed a cross-resistance study using a panel of 63 viral strains from PI-experienced patients selected for the presence of primary PI mutations known to confer resistance to multiple PIs now in clinical use. The results showed that PL-100 retained excellent antiviral activity against almost all of these PI-resistant viruses and that its performance in this regard was superior to those of atazanavir, amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir. In almost every case, the increase in the EC50 for PL-100 observed with viruses containing multiple mutations in protease was far less than that obtained with the other drugs tested. These data underscore the potential for PL-100 to be used in the treatment of drug-resistant HIV disease and argue for its further development.

scholarly journals Soluble Glycosaminoglycans Do Not Potentiate RANTES Antiviral Activity on the Infection of Primary Macrophages by Human Immunodeficiency Virus Type 1

Virology ◽  
2000 ◽  
Vol 278 (2) ◽  
pp. 412-422 ◽  
Author(s):  
Loyda Ylisastigui ◽  
Youssef Bakri ◽  
Saaïd Amzazi ◽  
Jean Claude Gluckman ◽  
Abdelaziz Benjouad
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus

scholarly journals Dendritic Cell Precursors Are Permissive to Dengue Virus and Human Immunodeficiency Virus Infection

2005 ◽  
Vol 79 (12) ◽  
pp. 7291-7299 ◽  
Author(s):  
Wing-Hong Kwan ◽  
Anna-Marija Helt ◽  
Concepción Marañón ◽  
Jean-Baptiste Barbaroux ◽  
Anne Hosmalin ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Dengue Virus ◽  
Blood Monocytes ◽  
Dengue Virus Infection ◽  
Differentiation Potential ◽  
Antiviral Immune Response ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT CD14+ interstitial cells reside beneath the epidermis of skin and mucosal tissue and may therefore play an important role in viral infections and the shaping of an antiviral immune response. However, in contrast to dendritic cells (DC) or blood monocytes, these antigen-presenting cells (APC) have not been well studied. We have previously described long-lived CD14+ cells generated from CD34+ hematopoietic progenitors, which may represent model cells for interstitial CD14+ APC. Here, we show that these cells carry DC-SIGN and differentiate into immature DC in the presence of granulocyte-macrophage colony-stimulating factor. We have compared the CD14+ cells and the DC derived from these cells with respect to dengue virus and human immunodeficiency virus type 1 (HIV-1) infection. Both cell types are permissive to dengue virus infection, but the CD14+ cells secrete the anti-inflammatory cytokine interleukin 10 and no tumor necrosis factor alpha. Regarding HIV, the CD14+ cells are permissive to HIV-1, release higher p24 levels than the derived DC, and more efficiently activate HIV Pol-specific CD8+ memory T cells. The CD14+ DC precursors infected with either virus retain their DC differentiation potential. The results suggest that interstitial CD14+ APC may contribute to HIV-1 and dengue virus infection and the shaping of an antiviral immune response.

scholarly journals Human Immunodeficiency Virus Type 1 Escapes from RNA Interference-Mediated Inhibition

2004 ◽  
Vol 78 (5) ◽  
pp. 2601-2605 ◽  
Author(s):  
Atze T. Das ◽  
Thijn R. Brummelkamp ◽  
Ellen M. Westerhout ◽  
Monique Vink ◽  
Mandy Madiredjo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Rna Interference ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Antiviral Drug ◽  
Target Sequence ◽  
Small Interfering Rnas ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Short-term assays have suggested that RNA interference (RNAi) may be a powerful new method for intracellular immunization against human immunodeficiency virus type 1 (HIV-1) infection. However, RNAi has not yet been shown to protect cells against HIV-1 in long-term virus replication assays. We stably introduced vectors expressing small interfering RNAs (siRNAs) directed against the HIV-1 genome into human T cells by retroviral transduction. We report here that an siRNA directed against the viral Nef gene (siRNA-Nef) confers resistance to HIV-1 replication. This block in replication is not absolute, and HIV-1 escape variants that were no longer inhibited by siRNA-Nef appeared after several weeks of culture. These RNAi-resistant viruses contained nucleotide substitutions or deletions in the Nef gene that modified or deleted the siRNA-Nef target sequence. These results demonstrate that efficient inhibition of HIV-1 replication through RNAi is possible in stably transduced cells. Therefore, RNAi could become a realistic gene therapy approach with which to overcome the devastating effect of HIV-1 on the immune system. However, as is known for antiviral drug therapy against HIV-1, antiviral approaches involving RNAi should be used in a combined fashion to prevent the emergence of resistant viruses.

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