viral inhibitor
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2021 ◽  
Vol 22 (21) ◽  
pp. 11869
Author(s):  
Qiaoshuai Lan ◽  
Chao Wang ◽  
Jie Zhou ◽  
Lijue Wang ◽  
Fanke Jiao ◽  
...  

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.


Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1707
Author(s):  
Pratyusha Mandal ◽  
Lynsey N. Nagrani ◽  
Liliana Hernandez ◽  
Anita Louise McCormick ◽  
Christopher P. Dillon ◽  
...  

Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochondrial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially deflected receptor-interacting protein kinase (RIPK)3-dependent necroptosis, the most potent of the three cell death pathways. This process remained independent of caspase-8, although suppression of this apoptotic protease enhances necroptosis in most cell types. Second, the virus deflected TNF-mediated extrinsic apoptosis, a pathway dependent on autocrine TNF production by macrophages that proceeds independently of mitochondrial death machinery or RIPK3. Third, cytomegalovirus deflected BCL-2 family protein-dependent mitochondrial cell death through combined TNF-dependent and -independent signaling even in the absence of RIPK1, RIPK3, and caspase-8. Furthermore, each of these cell death pathways dictated a distinct pattern of cytokine and chemokine activation. Therefore, cytomegalovirus employs sequential, non-redundant suppression strategies to specifically modulate the timing and execution of necroptosis, extrinsic apoptosis, and intrinsic apoptosis within infected cells to orchestrate virus control and infection-dependent inflammation. Virus-encoded death suppressors together hold control over an intricate network that upends host defense and supports pathogenesis in the intact mammalian host.


2021 ◽  
Vol 33 (10) ◽  
pp. 2301-2305
Author(s):  
K. Bhargavi ◽  
P. Shyamala ◽  
G. Nageswara Rao

Protonation constants of a viral inhibitor, aurintricarboxylic acid were determined using potentiometric method of data acquisition followed by chemometric modelling methods of analysis in the presence of two different kinds of micellar media, CTAB, a cationic micelle and SDS, an anionic micelle. MINIQUAD75 program was used for the determination of the plausible species and their corresponding formation constants at 303 ± 0.1 K and 0.01 M ionic strength. Five formation constants were identified corresponding to five ionizable hydrogens. Species concentration distribution diagrams were generated using Origin software. Best-fit chemical models were selected on the basis of statistical parameters like standard deviation (SD), U (sum of the squares of the residuals in mass balance equations) and chi-square test. It was found that the formation constants are lower in CTAB micellar medium while there is no significant change in the presence of SDS compared to aqueous medium.


2021 ◽  
Author(s):  
Nur Awaliah ◽  
Nunuk Hariani Soekamto ◽  
Firdaus ◽  
Felycitae Ekalaya Appa ◽  
Septaria Yolan Kalalinggi

2020 ◽  
Vol 50 (9) ◽  
Author(s):  
Sydnei Dionisio Batista de Almeida ◽  
Daniel Andrade de Siqueira Franco ◽  
Antonio Luiz Cerdeira ◽  
Sonia Claudia do Nascimento de Queiroz ◽  
Marcus Barifouse Matallo

ABSTRACT: Shikimic acid (SA) has witnessed a strong increase in recent years due to the increasing demand of the pharmaceutical and cosmetic industry. The SA is used as a precursor for the synthesis of oseltamivir phosphate (Tamiflu®), a potent viral inhibitor and is extracted from the plant Illicium verum Hook which has a limited availability. This article proposed the use of Urochloa plantaginea (Link.) webster and glyphosate, as an alternative source of SA. U. plantaginea plants with 3 - 4 tillers and 4 - 6 leaves were harvest at 3, 6, 9 and 12 days after application (DAT) of low rates of glyphosate. Samples were dried, extracted, analyzed by HPLC and LC-MS/MS. The maximum SA concentrations were observed at 6 days after glyphosate at 36 g.a.e.ha-1 was applied in plants of U. plantaginea with 4 to 6 leaves. The capability of this annual gramineae to produce elevated SA levels throughout the entire biomass affords its potential for a greater yield on a per hectare basis.


2016 ◽  
Vol 91 (3) ◽  
Author(s):  
Sonja M. Best

ABSTRACT The vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. Their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with Zika virus (ZIKV) or West Nile virus in the Americas. Every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to ZIKV, antagonizes the host type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting that suppression of this pathway is an important determinant of infection. The most direct and potent viral inhibitor of this pathway is the nonstructural protein NS5. However, the mechanisms utilized by NS5 from different flaviviruses are often quite different, sometimes despite close evolutionary relationships between viruses. The varied mechanisms of NS5 as an IFN-I antagonist are also surprising given that the evolution of NS5 is restrained by the requirement to maintain function of two enzymatic activities critical for virus replication, the methyltransferase and RNA-dependent RNA polymerase. This review discusses the different strategies used by flavivirus NS5 to evade the antiviral effects of IFN-I and how this information can be used to better model disease and develop antiviral countermeasures.


2016 ◽  
Vol 23 (4) ◽  
pp. 358-358
Author(s):  
Rutger D Luteijn ◽  
Emmanuel J H J Wiertz
Keyword(s):  

2016 ◽  
Vol 23 (2) ◽  
pp. 95-97 ◽  
Author(s):  
Rutger D Luteijn ◽  
Emmanuel J H J Wiertz
Keyword(s):  

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Nicole A. Tillie ◽  
Jayson L. Parker ◽  
Jordan J. Feld

Background and Aims.This study analyzed the risk of clinical trial failure of new drugs for hepatitis C between January 1998 and January 2015.Methods.Hepatitis C drug development trials that were in phases I–III of clinical trial testing were obtained from the publicly accessible clinical trial repository and other publicly available databases. Drug compounds were excluded from the study if they began their phase I testing before 1998, if they were not industry sponsored, or if they treated secondary complications of hepatitis C. Clinical trial success rates were analyzed in comparison to industry expectations. Further analysis was conducted on the molecule classifications, the mechanisms of action, and the trial endpoints.Results.One hundred and twenty-three unique drug compounds were found to fulfill the inclusion criteria, eight of which had FDA approval. The overall cumulative pass rate for hepatitis C drugs was 20%, which is double the industry expectation rate. Viral inhibitor small molecule drugs significantly reduced the risk of drug failure during clinical trials compared to other mechanisms of action.Conclusion.On average, one in every five drugs that began clinical testing will be approved for market. Viral inhibitor small molecule drugs are the most promising and hold the least risk.


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