scholarly journals Biocomputational Screening and Pharmacological Studies of Gymnema sylvester in Contrast to Human CCR5 and CXCR4 Chemokine Receptors

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kavitapu VV ◽  
◽  
Sharma S ◽  
Keyword(s):  
Side Effects ◽  
Chemokine Receptors ◽  
Antiviral Drug ◽  
Treatment Strategies ◽  
Binding Activity ◽  
Viral Envelope ◽  
Gymnema Sylvestre ◽  
Highly Active ◽  
Global Threat ◽  
Hiv 1

Viral diseases have remained a major global threat regardless of significant advances in therapeutic and treatment strategies. The advancement of viral resistance to drugs, along with several side effects, has resulted in critical medical issues, especially when administered in combination for extended treatment periods. Natural product-based therapies for the health of humans are associated with lower toxicity and fewer side effects. Virtual in-silico screening has been shown to be effective in addressing the unique challenges of antiviral drug development, making the process quicker, safer and less expensive. Novel ligands are evolving as potential agents, which are efficient in blocking virus–cell fusion to surpass the main disadvantages of traditional Highly Active Antiretroviral (HAART) drugs used in HIV-1 infection. The plant Gymnema sylvestre contains various bioactive compounds with medicinal properties. The HIV entry process can be blocked during the binding activity of glycoprotein gp120 viral envelope to one of the two receptors CXCR4 or CCR5 and binding to both the CD4 receptors. The significance of chemokine receptors as an anti- HIV target depends on the fact that they are involved in the entry of the virus into the cell at the early stages. Thus, the HIV/coreceptor relationship has emerged as a key focus for developing new antiviral strategies for the prevention and also treatment of HIV infection. In the present study, the phytochemicals selected from Gymnema sylvestre were subjected to ADME analysis. This was followed by the molecular docking analysis and MD simulation to estimate the selected ligands drug likeness, which may serve as new leads for the cure of HIV-1 infections.

EXPERIENCE WITH THE USE OF ALUVIA IN THE TREATMENT OF PATIENTS WITH MODERATE COVID-19

2021 ◽  
pp. 4-8
Author(s):  
Б. Б. Кошкимбаев ◽  
А. Ж. Кунградбаева ◽  
Б. А. Сахиева
Keyword(s):  
Antiviral Drug ◽  
Scientific Paper ◽  
Antiretroviral Drugs ◽  
Hiv Protease ◽  
Highly Active ◽  
Coronavirus Infection ◽  
Infection Cycles ◽  
Hiv 1 ◽  
Aspartyl Proteases

В настоящее время этиологическое лечение корона вирусной инфекции COVID-19 SARS CoV-2 не выявлено. Было исследовано влияние различных групп противовирусных препаратов на коронавирус. В ряде стран активно применялся лекарственный препарат Алувиа против коронавируса (комбинированный лопинавир и ритонавир). В данной научной работе представлены результаты применения высоко активных антиретро вирусных препаратов при коронавирусной инфекции.Лопинавир - ингибитор протеаз ВИЧ-1 и ВИЧ-2 - предотвращает расщепление gagpol-полипротеина, приводя к продукции незрелого неинфекционного вируса. Ритонавир - пептидомиметический ингибитор ВИЧ-1 и ВИЧ-2 аспартил протеаз. Торможение ВИЧ-протеазы делает этот фермент неспособным к обработке предшественника gag pol полипротеина, что приводит к образованию морфологически незрелых ВИЧ частиц, не способных к инициированию новых циклов инфицирования. [1] Currently, no etiological treatment of COVID-19 SARS CoV-2 coronavirus infection has been identified. The influence of various antiviral drug groups on the coronavirus was studied. One of them is the drug lopinavir \\ritonavir. This scientific paper presents an analysis of the experience of using highly active antiretroviral drugs in coronavirus infection. Lopinaviran inhibitor of HIV-1 and HIV - 2 proteases prevents the cleavage of gagpolpolyprotein, leading to the production of an immature noninfectious virus.Ritonavir is a peptidomimetic inhibitor of HIV-1 and HIV-2 aspartyl proteases. Inhibition of HIV protease makes this enzyme unable to process the gag pol precursor polyprotein, which leads to the formation of morphologically immature HIV particles that are not able to initiate new infection cycles. [1]

scholarly journals Staphylococcus aureus Leukocidin LukED and HIV-1 gp120 Target Different Sequence Determinants on CCR5

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Kayan Tam ◽  
Megan Schultz ◽  
Tamara Reyes-Robles ◽  
Bénédicte Vanwalscappel ◽  
Joshua Horton ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Chemokine Receptors ◽  
Point Mutations ◽  
Cell Lysis ◽  
Vital Role ◽  
Viral Envelope ◽  
Host Cells ◽  
Mediate Cytotoxicity ◽  
Necessary And Sufficient ◽  
Hiv 1

ABSTRACT Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry. These analyses showed that the second and third extracellular loops (ECL) of CCR5 are necessary and sufficient for LukED to target the receptor and promote cell lysis. In contrast, the second ECL of CCR5 is necessary but not sufficient for HIV-1 infectivity. The analysis of CCR5 point mutations showed that glycine-163 is critical for HIV-1 infectivity, while arginine-274 and aspartic acid-276 are critical for LukED cytotoxicity. Point mutations in ECL2 diminished both HIV-1 infectivity and LukED cytotoxicity. Treatment of cells with LukED did not interfere with CCR5-tropic HIV-1 infectivity, demonstrating that LukED and the viral envelope glycoprotein use nonoverlapping sites on CCR5. Analysis of point mutations in LukE showed that amino acids 64 to 69 in the rim domain are required for CCR5 targeting and cytotoxicity. Taking the results together, this study identified the molecular basis by which LukED targets CCR5, highlighting the divergent molecular interactions evolved by HIV-1 and LukED to interact with CCR5. IMPORTANCE The bicomponent pore-forming toxins are thought to play a vital role in the success of Staphylococcus aureus as a mammalian pathogen. One of the leukocidins, LukED, is necessary and sufficient for lethality in mice. At the molecular level, LukED causes cell lysis through binding to specific cellular receptors. CCR5 is one of the receptors targeted by LukED and is the major coreceptor for CCR5-tropic HIV-1. While the molecular interaction of CCR5 and HIV-1 is well characterized, the means by which LukED interacts with CCR5 is less clear. In this study, we demonstrated that receptor specificity is conferred through unique interactions between key domains on CCR5 and LukE. Although HIV-1 and LukED target the same receptor, our data demonstrated that they interact with CCR5 differently, highlighting the molecular complexity of host-pathogen interactions.

scholarly journals DC-SIGN and CLEC-2 Mediate Human Immunodeficiency Virus Type 1 Capture by Platelets

2006 ◽  
Vol 80 (18) ◽  
pp. 8951-8960 ◽  
Author(s):  
Chawaree Chaipan ◽  
Elizabeth J. Soilleux ◽  
Peter Simpson ◽  
Heike Hofmann ◽  
Thomas Gramberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Binding Activity ◽  
Viral Envelope ◽  
Viral Envelope Protein ◽  
Immunodeficiency Virus ◽  
Attachment Factor ◽  
Hiv 1

ABSTRACT Platelets can engulf human immunodeficiency virus type 1 (HIV-1), and a significant amount of HIV-1 in the blood of infected individuals is associated with these cells. However, it is unclear how platelets capture HIV-1 and whether platelet-associated virus remains infectious. DC-SIGN and other lectins contribute to capture of HIV-1 by dendritic cells (DCs) and facilitate HIV-1 spread in DC/T-cell cocultures. Here, we show that platelets express both the C-type lectin-like receptor 2 (CLEC-2) and low levels of DC-SIGN. CLEC-2 bound to HIV-1, irrespective of the presence of the viral envelope protein, and facilitated HIV-1 capture by platelets. However, a substantial fraction of the HIV-1 binding activity of platelets was dependent on DC-SIGN. A combination of DC-SIGN and CLEC-2 inhibitors strongly reduced HIV-1 association with platelets, indicating that these lectins are required for efficient HIV-1 binding to platelets. Captured HIV-1 was maintained in an infectious state over several days, suggesting that HIV-1 can escape degradation by platelets and might use these cells to promote its spread. Our results identify CLEC-2 as a novel HIV-1 attachment factor and provide evidence that platelets capture and transfer infectious HIV-1 via DC-SIGN and CLEC-2, thereby possibly facilitating HIV-1 dissemination in infected patients.

scholarly journals V3 Recombinants Indicate a Central Role for CCR5 as a Coreceptor in Tissue Infection by Human Immunodeficiency Virus Type 1

1999 ◽  
Vol 73 (3) ◽  
pp. 2350-2358 ◽  
Author(s):  
Stephen Y. Chan ◽  
Roberto F. Speck ◽  
Christopher Power ◽  
Sarah L. Gaffen ◽  
Bruce Chesebro ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Chemokine Receptors ◽  
Viral Envelope ◽  
Tissue Infection ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 to both CD4 and one of several chemokine receptors (coreceptors) permits entry of virus into target cells. Infection of tissues may establish latent viral reservoirs as well as cause direct pathologic effects that manifest as clinical disease such as HIV-associated dementia. We sought to identify the critical coreceptors recognized by HIV-1 tissue-derived strains as well as to correlate these coreceptor preferences with site of infection and dementia diagnosis. To reconstitute coreceptor use, we cloned HIV-1 envelope V3 sequences encoding the primary determinants of coreceptor specificity from 13 brain-derived and 6 colon-derived viruses into an isogenic (NL4-3) viral background. All V3 recombinants utilized the chemokine receptor CCR5 uniformly and efficiently as a coreceptor but not CXCR4, BOB/GPR15, or Bonzo/STRL33. Other receptors such as CCR3, CCR8, and US28 were inefficiently and variably used as coreceptors by various envelopes. CCR5 without CD4 present did not allow for detectable infection by any of the tested recombinants. In contrast to the pathogenic switch in coreceptor specificity frequently observed in comparisons of blood-derived viruses early after HIV-1 seroconversion and after onset of AIDS, the characteristics of these V3 recombinants suggest that CCR5 is a primary coreceptor for brain- and colon-derived viruses regardless of tissue source or diagnosis of dementia. Therefore, tissue infection may not depend significantly on viral envelope quasispeciation to broaden coreceptor range but rather selects for CCR5 use throughout disease progression.

Recent Progress in the Development of HIV-1 Entry Inhibitors: From Small Molecules to Potent Anti-HIV Agents

2019 ◽  
Vol 19 (18) ◽  
pp. 1599-1620 ◽  
Author(s):  
Khomson Suttisintong ◽  
Narongpol Kaewchangwat ◽  
Eknarin Thanayupong ◽  
Chakkrapan Nerungsi ◽  
Onsiri Srikun ◽  
...  
Keyword(s):  
Host Cell ◽  
Viral Entry ◽  
Chemokine Receptors ◽  
Recent Progress ◽  
Viral Envelope ◽  
Surface Glycoprotein ◽  
Entry Inhibitors ◽  
Transmembrane Glycoprotein ◽  
Glycoprotein Gp120 ◽  
Hiv 1

Viral entry, the first process in the reproduction of viruses, primarily involves attachment of the viral envelope proteins to membranes of the host cell. The crucial components that play an important role in viral entry include viral surface glycoprotein gp120, viral transmembrane glycoprotein gp41, host cell glycoprotein (CD4), and host cell chemokine receptors (CCR5 and CXCR4). Inhibition of the multiple molecular interactions of these components can restrain viruses, such as HIV-1, from fusion with the host cell, blocking them from reproducing. This review article specifically focuses on the recent progress in the development of small-molecule HIV-1 entry inhibitors and incorporates important aspects of their structural modification that lead to the discovery of new molecular scaffolds with more potency.

scholarly journals Molecular Understanding of HIV-1 Latency

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
W. Abbas ◽  
G. Herbein
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Viral Production ◽  
Virus Eradication ◽  
Highly Active ◽  
Special Concern ◽  
Memory Cd4 T Cells ◽  
Haart Interruption ◽  
Hiv 1

The introduction of highly active antiretroviral therapy (HAART) has been an important breakthrough in the treatment of HIV-1 infection and has also a powerful tool to upset the equilibrium of viral production and HIV-1 pathogenesis. Despite the advent of potent combinations of this therapy, the long-lived HIV-1 reservoirs like cells from monocyte-macrophage lineage and resting memory CD4+ T cells which are established early during primary infection constitute a major obstacle to virus eradication. Further HAART interruption leads to immediate rebound viremia from latent reservoirs. This paper focuses on the essentials of the molecular mechanisms for the establishment of HIV-1 latency with special concern to present and future possible treatment strategies to completely purge and target viral persistence in the reservoirs.

In vitro binding activity between HCK SH3 domain and HIV-1 Nef protein

2011 ◽  
Vol 31 (3) ◽  
pp. 262-265
Author(s):  
Xiao-lin QIN ◽  
Chao-qi LIU ◽  
Dong-ming REN ◽  
Yong-qin ZHOU
Keyword(s):  
Sh3 Domain ◽  
Binding Activity ◽  
Hiv 1

Using Naïve Bayes Algorithm to Estimate the Response to Drug in Lung Cancer Patients

2019 ◽  
Vol 21 (10) ◽  
pp. 734-748 ◽  
Author(s):  
Baoling Guo ◽  
Qiuxiang Zheng
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Drug Response ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Cancer Resistance ◽  
Lung Cancer Patients ◽  
Bayes Algorithm

Aim and Objective: Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method: Clinical patients with lung cancer do not have yet particularly effective treatment options, while patients with lung cancer resistance not only delayed the treatment cycle but also caused strong side effects. Therefore, if we can sum up the abnormalities of functional level from the molecular level, we can scientifically and effectively evaluate the patients' sensitivity to treatment and make the personalized treatment strategies to avoid the side effects caused by over-treatment and improve the prognosis. Result & Conclusion: According to the different sensitivities of lung cancer patients to drug response, this study screened out genes that were significantly associated with drug resistance. The bayes model was used to assess patient resistance.

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