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https://read.qxmd.com/read/30896149/treatment-of-chronic-hepatitis-b-virus-infection-using-small-molecule-modulators-of-nucleocapsid-assembly-recent-advances-and-perspectives
#1
Li Yang, Feifei Liu, Xiankun Tong, Daniel Hoffmann, Jianping Zuo, Mengji Lu
Based on the recent advance of basic research on molecular biology of hepatitis B virus (HBV) infection, novel antiviral drugs targeting various steps of HBV life cycle are developed in recent years. HBV nucleocapsid assembly is now recognized as a hot target for anti-HBV drug development. Structural and functional analysis of HBV nucleocapsid allowed rational design and improvement of small molecules with the ability to interact with the components of HBV nucleocapsid and modulate the viral nucleocapsid assembly process...
March 21, 2019: ACS Infectious Diseases
https://read.qxmd.com/read/30895392/safe-travel-preparation-for-hiv-infected-patients
#2
REVIEW
David Mariano, Darvin Scott Smith
PURPOSE OF REVIEW: Infectious diseases are a risk when traveling internationally, and it is important to know the potential disease burden of a region and take appropriate preventative actions before traveling. For individuals with HIV, there are special considerations and contradictions for various vaccines and medications as well as interactions with likely antiviral drugs. The purpose of this review is to summarize the vaccine and medication recommendations for travelers with HIV infection...
March 20, 2019: Current Infectious Disease Reports
https://read.qxmd.com/read/30893774/ebola-virus-entry-from-molecular-characterization-to-drug-discovery
#3
REVIEW
Cristiano Salata, Arianna Calistri, Gualtiero Alvisi, Michele Celestino, Cristina Parolin, Giorgio Palù
Ebola Virus Disease (EVD) is one of the most lethal transmissible infections, characterized by a high fatality rate, and caused by a member of the Filoviridae family. The recent large outbreak of EVD in Western Africa (2013⁻2016) highlighted the worldwide threat represented by the disease and its impact on global public health and the economy. The development of highly needed anti-Ebola virus antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro , allowing to screen for potential active compounds outside a biosafety level-4 (BSL-4) containment...
March 19, 2019: Viruses
https://read.qxmd.com/read/30886338/anti-hiv-1-integrase-potency-of-methylgallate-from-alchornea-cordifolia-using-in-vitro-and-in-silico-approaches
#4
Xavier Siwe-Noundou, Thommas M Musyoka, Vuyani Moses, Derek T Ndinteh, Dumisani Mnkandhla, Heinrich Hoppe, Özlem Tastan Bishop, Rui W M Krause
According to the 2018 report of the United Nations Programme on HIV/AIDS (UNAIDS), acquired immune deficiency syndrome (AIDS), a disease caused by the human immunodeficiency virus (HIV), remains a significant public health problem. The non-existence of a cure or effective vaccine for the disease and the associated emergence of resistant viral strains imply an urgent need for the discovery of novel anti-HIV drug candidates. The current study aimed to identify potential anti-retroviral compounds from Alchornea cordifolia...
March 18, 2019: Scientific Reports
https://read.qxmd.com/read/30885750/potent-and-broad-spectrum-cycloheptathiophene-3-carboxamide-compounds-that-target-the-pa-pb1-interaction-of-influenza-virus-rna-polymerase-and-possess-a-high-barrier-to-drug-resistance
#5
Giulio Nannetti, Serena Massari, Beatrice Mercorelli, Chiara Bertagnin, Jenny Desantis, Giorgio Palù, Oriana Tabarrini, Arianna Loregian
Influenza viruses are major respiratory pathogens responsible for both seasonal epidemics and occasional pandemics worldwide. The current available treatment options have limited efficacy and thus the development of new antivirals is highly needed. We previously reported the identification of a series of cycloheptathiophene-3-carboxamide compounds as influenza A virus inhibitors that act by targeting the protein-protein interactions between the PA-PB1 subunits of the viral polymerase. In this study, we characterized the antiviral properties of the most promising compounds as well as investigated their propensity to induce drug resistance...
March 15, 2019: Antiviral Research
https://read.qxmd.com/read/30876974/dna-polymerase-%C3%AE-hypothesis-in-nucleoside-reverse-transcriptase-induced-mitochondrial-toxicity-revisited-a-potentially-protective-role-for-citrus-fruit-derived-naringenin
#6
REVIEW
Mathabo Ruth Lutu, Sanelisiwe Nzuza, Pascale Edith Mofo Mato, Khmera Govender, Londiwe Mphumelelo Gumede, Sinenhlanhla Innocentia Kumalo, Nontokozo Nomfundo Mlambo, Ranjendraparsad Hurchund, Peter Mark Oroma Owira
Nucleoside reverse transcriptase inhibitors (NRTIs) form the backbone in combination antiretroviral therapy (cARVs). They halt chain elongation of the viral cDNA by acting as false substrates in counterfeit incorporation mechanism to viral RNA-dependent DNA polymerase. In the process genomic DNA polymerase as well as mitochondrial DNA (mtDNA) polymerase-γ (which has a much higher affinity for these drugs at therapeutic doses) are also impaired. This leads to mitochondrial toxicity that manifests clinically as mitochondrial myopathy, peripheral neuropathy, hyperlactatemia or lactic acidosis and lipoatrophy...
March 12, 2019: European Journal of Pharmacology
https://read.qxmd.com/read/30875748/enhanced-autophagy-contributes-to-reduced-viral-infection-in-black-flying-fox-cells
#7
Eric D Laing, Spencer L Sterling, Dawn L Weir, Chelsi R Beauregard, Ina L Smith, Sasha E Larsen, Lin-Fa Wang, Andrew L Snow, Brian C Schaefer, Christopher C Broder
Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus⁻host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian bat lyssavirus (ABLV) infection, viral replication is dampened in these bat cells...
March 14, 2019: Viruses
https://read.qxmd.com/read/30871179/recent-updates-on-mouse-models-for-human-immunodeficiency-influenza-and-dengue-viral-infections
#8
REVIEW
Vinodhini Krishnakumar, Siva Sundara Kumar Durairajan, Kalichamy Alagarasu, Min Li, Aditya Prasad Dash
Well-developed mouse models are important for understanding the pathogenesis and progression of immunological response to viral infections in humans. Moreover, to test vaccines, anti-viral drugs and therapeutic agents, mouse models are fundamental for preclinical investigations. Human viruses, however, seldom infect mice due to differences in the cellular receptors used by the viruses for entry, as well as in the innate immune responses in mice and humans. In other words, a species barrier exists when using mouse models for investigating human viral infections...
March 13, 2019: Viruses
https://read.qxmd.com/read/30871092/novel-therapeutics-for-epstein%C3%A2-barr-virus
#9
REVIEW
Graciela Andrei, Erika Trompet, Robert Snoeck
Epstein⁻Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35⁻50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo...
March 12, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/30867304/design-and-characterization-of-cholesterylated-peptide-hiv-1-2-fusion-inhibitors-with-extremely-potent-and-long-lasting-antiviral-activity
#10
Yuanmei Zhu, Huihui Chong, Danwei Yu, Yan Guo, Yusen Zhou, Yuxian He
HIV infection requires lifelong treatment with multiple antiretroviral drugs in a combination, which ultimately causes cumulative toxicities and drug resistance, thus necessitating the development of novel antiviral agents. We recently found that enfuvirtide (T-20)-based lipopeptides conjugated with fatty acids have dramatically increased in vitro and in vivo anti-HIV activities. Herein, a group of cholesterol-modified fusion inhibitors were characterized with significant findings. First, novel cholesterylated inhibitors, such as LP-83 and LP-86, showed the most potent activity in inhibiting divergent HIV-1, HIV-2, and simian immunodeficiency virus (SIV)...
March 13, 2019: Journal of Virology
https://read.qxmd.com/read/30863536/emerging-small-molecule-treatments-for-multiple-sclerosis-focus-on-b-cells
#11
REVIEW
Aaron Gregson, Kaitlyn Thompson, Stella E Tsirka, David L Selwood
Multiple sclerosis (MS) is a major cause of disability in young adults. Following an unknown trigger (or triggers), the immune system attacks the myelin sheath surrounding axons, leading to progressive nerve cell death. Antibodies and small-molecule drugs directed against B cells have demonstrated good efficacy in slowing progression of the disease. This review focusses on small-molecule drugs that can affect B-cell biology and may have utility in disease management. The risk genes for MS are examined from the drug target perspective...
2019: F1000Research
https://read.qxmd.com/read/30863136/precision-medicine-retrospective-chart-review-and-data-analysis-of-200-patients-on-dapsone-combination-therapy-for-chronic-lyme-disease-post-treatment-lyme-disease-syndrome-part-1
#12
Richard I Horowitz, Phyllis R Freeman
Purpose: We collected data from an online survey of 200 of our patients, which evaluated the efficacy of dapsone (diaminodiphenyl sulfone, ie, DDS) combined with other antibiotics and agents that disrupt biofilms for the treatment of chronic Lyme disease/post-treatment Lyme disease syndrome (PTLDS). We also collected aggregate data from direct retrospective chart review, including laboratory testing for Lyme, other infections, and associated tick-borne coinfections. This helped us to determine the frequency of exposure to other infections/coinfections among a cohort of chronically ill Lyme patients, evaluate the efficacy of newer "persister" drug regimens like DDS, and determine how other infections and tick-borne coinfections may be contributing to the burden of chronic illness leading to resistant symptomatology...
2019: International Journal of General Medicine
https://read.qxmd.com/read/30862061/gene-therapy-approaches-to-functional-cure-and-protection-of-hematopoietic-potential-in-hiv-infection
#13
REVIEW
Tetsuo Tsukamoto
Although current antiretroviral drug therapy can suppress the replication of human immunodeficiency virus (HIV), a lifelong prescription is necessary to avoid viral rebound. The problem of persistent and ineradicable viral reservoirs in HIV-infected people continues to be a global threat. In addition, some HIV-infected patients do not experience sufficient T-cell immune restoration despite being aviremic during treatment. This is likely due to altered hematopoietic potential. To achieve the global eradication of HIV disease, a cure is needed...
March 11, 2019: Pharmaceutics
https://read.qxmd.com/read/30854283/transcriptional-and-post-transcriptional-regulation-of-viral-gene-expression-in-the-gamma-herpesvirus-kaposi-s-sarcoma-associated-herpesvirus
#14
Matthew Butnaru, Marta M Gaglia
Purpose of review: Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of the AIDS-associated tumor Kaposi's sarcoma, is a complex virus that expresses ~90 proteins in a regulated temporal cascade during its replication cycle. Although KSHV relies on cellular machinery for gene expression, it also uses specialized regulators to control nearly every step of the process. In this review we discuss the current understanding of KSHV gene regulation. Recent findings: High-throughput sequencing and a new robust system to mutate KSHV have paved the way for comprehensive studies of KSHV gene expression, leading to the characterization of new viral factors that control late gene expression and post-transcriptional steps of gene regulation...
December 2018: Current Clinical Microbiology Reports
https://read.qxmd.com/read/30853381/stearoyl-coa-desaturase-1-is-required-for-flavivirus-rna-replication
#15
Takayuki Hishiki, Fumihiro Kato, Yasunori Nio, Satoru Watanabe, Nicole Wei Wen Tan, Daisuke Yamane, Yasuyuki Miyazaki, Chun-Chieh Lin, Rieko Suzuki, Shigeru Tajima, Chang-Kweng Lim, Masayuki Saijo, Makoto Hijikata, Subhash G Vasudevan, Tomohiko Takasaki
Dengue virus (DENV) is the most prevalent human arthropod-borne virus and causes severe problems worldwide, mainly in tropical and sub-tropical regions. However, there is no specific antiviral drug against DENV infection. We and others recently reported that stearoyl-CoA desaturase-1 (SCD1) inhibitor showed potent suppression of hepatitis C virus replication. In this study, we examined the impact of SCD1 on DENV replication. We found that SCD1 inhibitors (MK8245 and #1716) dramatically suppressed DENV replication in a dose-dependent manner without cytotoxicity...
March 7, 2019: Antiviral Research
https://read.qxmd.com/read/30851352/a-30-kda-polyethylene-glycol-enfuvirtide-complex-enhances-the-exposure-of-enfuvirtide-in-lymphatic-viral-reservoirs-in-rats
#16
Lisa M Kaminskas, Charlotte C Williams, Nathania J Leong, Linda J Chan, Neville J Butcher, Orlagh M Feeney, Christopher J H Porter, David Tyssen, Gilda Tachedjian, David B Ascher
HIV therapy with anti-retroviral drugs is limited by the poor exposure of viral reservoirs, such as lymphoid tissue, to these small molecule drugs. We therefore investigated the effect of PEGylation on the anti-retroviral activity and subcutaneous lymphatic pharmacokinetics of the peptide-based fusion inhibitor enfuvirtide in thoracic lymph duct cannulated rats. Conjugation to a single 5 kDa linear PEG decreased anti-HIV activity three-fold compared to enfuvirtide. Whilst plasma and lymphatic exposure to peptide mass was moderately increased, the loss of anti-viral activity led to an overall decrease in exposure to enfuvirtide activity...
March 6, 2019: European Journal of Pharmaceutics and Biopharmaceutics
https://read.qxmd.com/read/30847961/toxic-myopathy-with-multiple-deletions-in-mitochondrial-dna-associated-with-long-term-use-of-oral-anti-viral-drugs-for-hepatitis-b-a-case-study
#17
Takayuki Fujii, Kei-Ichiro Takase, Hiroyuki Honda, Nobutoshi Kawamura, Ryo Yamasaki, Michiyo Urata, Takeshi Uchiumi, Toru Iwaki, Jun-Ichi Kira
Oral nucleoside analogs (NAs) reduce hepatitis B virus (HBV) replication by inhibiting HBV DNA polymerase. However, NAs can also affect human mitochondrial DNA (mtDNA) polymerase, which can lead to mtDNA depletion (quantitative abnormality). Indeed, several mitochondrial myopathy cases have been reported in which a reduced mtDNA copy number was induced by oral NAs for hepatitis B. Herein, we report a case of toxic myopathy with multiple mtDNA deletions (qualitative abnormality) associated with long-term use of NAs for hepatitis B...
March 7, 2019: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://read.qxmd.com/read/30845796/quantum-mechanics-molecular-mechanics-qm-mm-calculations-support-a-concerted-reaction-mechanism-for-the-zika-virus-ns2b-ns3-serine-protease-with-its-substrate
#18
Bodee Nutho, Adrian J Mulholland, Thanyada Rungrotmongkol
Zika virus (ZIKV) is mainly transmitted to humans by Aedes species mosquitoes and is associated with serious pathological disorders including microcephaly in newborns and Guillain-Barré syndrome in adults. Currently, there is no vaccine or anti-ZIKV drug available for preventing or controlling ZIKV infection. An attractive drug-target for ZIKV treatment is a two-compartment (NS2B/NS3) serine protease that processes viral polyprotein during infection. Here, conventional molecular dynamics (MD) simulations of the ZIKV protease in complex with peptide substrate (TGKRS) sequence at the C-terminus of NS2B show that the substrate is in the active conformation for cleavage reaction by ZIKV protease...
March 7, 2019: Journal of Physical Chemistry. B
https://read.qxmd.com/read/30842333/a-humanized-mouse-model-of-hiv-1-latency-with-enrichment-of-latent-virus-in-pd-1-and-tigit-cd4-t-cells
#19
George N Llewellyn, Eduardo Seclèn, Stephen Wietgrefe, Siyu Liu, Morgan Chateau, Hua Pei, Katherine Perkey, Matthew D Marsden, Sarah J Hinkley, David E Paschon, Michael C Holmes, Jerome A Zack, Stan G Louie, Ashley T Haase, Paula M Cannon
Combination anti-retroviral drug therapy (ART) potently suppresses HIV-1 replication but does not result in virus eradication or a cure. A major contributing factor is the long-term persistence of a reservoir of latently infected cells. To study this reservoir, we established a humanized mouse model of HIV-1 infection and ART suppression based on an oral ART regimen. Similar to humans, HIV-1 levels in the blood of ART-treated animals were frequently suppressed below the limits of detection. However, the limited timeframe of the mouse model and the small volume of available samples makes it a challenging model with which to achieve full viral suppression and to investigate the latent reservoir...
March 6, 2019: Journal of Virology
https://read.qxmd.com/read/30841485/terminase-large-subunit-provides-a-new-drug-target-for-herpesvirus-treatment
#20
REVIEW
Linlin Yang, Qiao Yang, Mingshu Wang, Renyong Jia, Shun Chen, Dekang Zhu, Mafeng Liu, Ying Wu, Xinxin Zhao, Shaqiu Zhang, Yunya Liu, Yanling Yu, Ling Zhang, Xiaoyue Chen, Anchun Cheng
Herpesvirus infection is an orderly, regulated process. Among these viruses, the encapsidation of viral DNA is a noteworthy link; the entire process requires a powered motor that binds to viral DNA and carries it into the preformed capsid. Studies have shown that this power motor is a complex composed of a large subunit, a small subunit, and a third subunit, which are collectively known as terminase. The terminase large subunit is highly conserved in herpesvirus. It mainly includes two domains: the C-terminal nuclease domain, which cuts the viral concatemeric DNA into a monomeric genome, and the N-terminal ATPase domain, which hydrolyzes ATP to provide energy for the genome cutting and transfer activities...
March 5, 2019: Viruses
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