Drug-resistant Virus Research Articles

Global prevalence and phylogeny of hepatitis B virus (HBV) drug and vaccine resistance mutations.

Vaccination and anti‐viral therapy with nucleos(t)ide analogues (NAs) are key approaches to reducing the morbidity, mortality and transmission of hepatitis B virus (HBV) infection. However, the efficacy of these interventions may be reduced by the emergence of drug resistance‐associated mutations (RAMs) and/or vaccine escape mutations (VEMs). We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations. We analysed sequences downloaded from the HBV Database and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. We generated maximum likelihood phylogenetic trees and used treeBreaker to investigate the distribution and estimated the age of selected mutations across tree branches. RAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our data set, and a significantly higher rate in genotype C at 5.4% (60/1102, p = 0.0007). VEMs had an overall prevalence of 1.3% (37/2837) and had the highest prevalence in genotype C and in Asia at 2.2% (24/1102; p = 0.002) and 1.6% (34/2109; p = 0.009), respectively. Phylogenetic analysis suggested that RAM/VEMs can arise independently of treatment/vaccine exposure. In conclusion, HBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C. Screening for genotype and for resistance‐associated mutations may help to improve stratified patient treatment. As NAs and HBV vaccines are increasingly being deployed for HBV prevention and treatment, monitoring for resistance and advocating for better treatment regimens for HBV remains essential.

Machine Learning in Discovery of New Antivirals and Optimization of Viral Infections Therapy

Nowadays, computational approaches play an important role in the design of new drug-like compounds and optimization of pharmacotherapeutic treatment of diseases. The emerging growth of viral infections, including those caused by the Human Immunodeficiency Virus (HIV), Ebola virus, recently detected coronavirus, and some others, leads to many newly infected people with a high risk of death or severe complications. A huge amount of chemical, biological, clinical data is at the disposal of the researchers. Therefore, there are many opportunities to find the relationships between the particular features of chemical data and the antiviral activity of biologically active compounds based on machine learning approaches. Biological and clinical data can also be used for building models to predict relationships between viral genotype and drug resistance, which might help determine the clinical outcome of treatment. In the current study, we consider machine-learning approaches in the antiviral research carried out during the past decade. We overview in detail the application of machine-learning methods for the design of new potential antiviral agents and vaccines, drug resistance prediction, and analysis of virus-host interactions. Our review also covers the perspectives of using the machine-learning approaches for antiviral research, including Dengue, Ebola viruses, Influenza A, Human Immunodeficiency Virus, coronaviruses, and some others.

Primary HIV drug resistance among newly HIV type-1 diagnosed patients in St. Petersburg

There is concern that the widespread use of antiretroviral drugs (ARV) to treat human immunodeficiency virus 1 (HIV-1) infection may result in the emergence of transmission of drug-resistant virus among persons newly infected with HIV-1. Russia is one of a growing number of countries in the world where drug-resistant HIV is becoming a serious health problem because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level.Materials and methods.We performed a genetic analysis of the HIV-1 plasma derived pol gene among the newly diagnosed ART-naïve HIV-1 infected patients during the period from November 2018 to October 2019 in the St. Petersburg Clinical Infectious Diseases Hospital named after S.P. Botkin. We used reverse transcriptase polymerase chain reaction (RT-PCR) followed by direct sequencing of PCR products to determine the prevalence of primary drug resistance (PDR) conferring mutations. HIV-1 genotypes were determined by phylogenetic analysis.Results.The predominant HIV-1 subtype was A1 (87.2%), followed by B (11.8%) and CRF06_cpx (1%). The overall prevalence of PDR was 11%. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors (NRTIs) was found in 8 individuals, to any non NRTIs in 5 subjects, and to any protease inhibitors in 1 case. Multidrug-resistant virus was identified in 2 individuals (2%).Conclusion.The distribution of HIV-1 genotypes in St. Petersburg, Russia is diverse. The emerging prevalence of PDR in ART-naïve patients demonstrates the significance of constant monitoring due to the challenges it presents towards treatment.

High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients.

Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified. Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care). Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL). Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens. Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor-based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL.

Antiviral Activity of Isoimperatorin Against Influenza A Virus in vitro and its Inhibition of Neuraminidase.

Influenza A virus (IAV) poses a severe threat to human health and is a major public health problem worldwide. As global anti-influenza virus drug resistance has increased significantly, there is an urgent need to develop new antiviral drugs, especially drugs from natural products. Isoimperatorin, an active natural furanocoumarin, exhibits a broad range of pharmacologic activities including anticoagulant, analgesic, anti-inflammatory, antibacterial, anti-tumor, and other pharmacological effects, so it has attracted more and more attention. In this study, the antiviral and mechanistic effects of isoimperatorin on influenza A virus in vitro were studied. Isoimperatorin illustrated a broad-spectrum antiviral effect, especially against the A/FM/1/47 (H1N1), A/WSN/33 (H1N1, S31N, amantadine resistant), A/Puerto Rico/8/34 (H1N1), and A/Chicken/Guangdong/1996 (H9N2) virus strains. The experimental results of different administration modes showed that isoimperatorin had the best antiviral activity under the treatment mode. Further time-of-addition experiment results indicated that when isoimperatorin was added at the later stage of the virus replication cycle (6–8 h, 8–10 h), it exhibited an effective antiviral effect, and the virus yield was reduced by 81.4 and 84.6%, respectively. In addition, isoimperatorin had no effect on the expression of the three viral RNAs (mRNA, vRNA, and cRNA). Both the neuraminidase (NA) inhibition assay and CETSA demonstrated that isoimperatorin exerts an inhibitory effect on NA-mediated progeny virus release. The molecular docking experiment simulated the direct interaction between isoimperatorin and NA protein amino acid residues. In summary, isoimperatorin can be used as a potential agent for the prevention and treatment of influenza A virus.

'Geno-to-pheno' SARS-CoV-2 genome-COVID-19 association studies

'Geno-to-pheno' SARS-CoV-2 genome-COVID-19 association studies

The shape of pleomorphic virions determines resistance to cell-entry pressure.

Many enveloped animal viruses produce a variety of particle shapes, ranging from small spherical to long filamentous types. Characterization of how the shape of the virion affects infectivity has been difficult because the shape is only partially genetically encoded, and most pleomorphic virus structures have no selective advantage in vitro. Here, we apply virus fractionation using low-force sedimentation, as well as antibody neutralization coupled with RNAScope, single-particle membrane fusion experiments and stochastic simulations to evaluate the effects of differently shaped influenza A viruses and influenza viruses pseudotyped with Ebola glycoprotein on the infection of cells. Our results reveal that the shape of the virus particles determines the probability of both virus attachment and membrane fusion when viral glycoprotein activity is compromised. The larger contact interface between a cell and a larger particle offers a greater probability that several active glycoproteins are adjacent to each other and can cooperate to induce membrane merger. Particles with a length of tens of micrometres can fuse even when 95% of the glycoproteins are inactivated. We hypothesize that non-genetically encoded variable particle shapes enable pleomorphic viruses to overcome selective pressure and may enable adaptation to infection of cells by emerging viruses such as Ebola. Our results suggest that therapeutics targeting filamentous virus particles could overcome antiviral drug resistance and immune evasion in pleomorphic viruses.

One-step vapor deposition of fluorinated polycationic coating to fabricate antifouling and anti-infective textile against drug-resistant bacteria and viruses.

The ongoing pandemic caused by the novel coronavirus has turned out to be one of the biggest threats to the world, and the increase of drug-resistant bacterial strains also threatens the human health. Hence, there is an urgent need to develop novel anti-infective materials with broad-spectrum anti-pathogenic activity. In the present study, a fluorinated polycationic coating was synthesized on a hydrophilic and negatively charged polyester textile via one-step initiated chemical vapor deposition of poly(dimethyl amino methyl styrene-co-1H,1H,2H,2H-perfluorodecyl acrylate) (P(DMAMS-co-PFDA), PDP). The surface characterization results of SEM, FTIR, and EDX demonstrated the successful synthesis of PDP coating. Contact angle analysis revealed that PDP coating endowed the polyester textile with the hydrophobicity against the attachment of different aqueous foulants such as blood, coffee, and milk, as well as the oleophobicity against paraffin oil. Zeta potential analysis demonstrated that the PDP coating enabled a transformation of negative charge to positive charge on the surface of polyester textile. The PDP coating exhibited excellent contact-killing activity against both gram-negative Escherichia coli and gram-positive methicillin-resistant Staphylococcus aureus, with the killing efficiency of approximate 99.9%. In addition, the antiviral capacity of PDP was determined by a green fluorescence protein (GFP) expression-based method using lentivirus-EGFP as a virus model. The PDP coating inactivated the negatively charged lentivirus-EGFP effectively. Moreover, the coating showed good biocompatibility toward mouse NIH 3T3 fibroblast cells. All the above properties demonstrated that PDP would be a promising anti-pathogenic polymeric coating with wide applications in medicine, hygiene, hospital, etc., to control the bacterial and viral transmission and infection.

Boronic acid-containing diarylpyrimidine derivatives as novel HIV-1 NNRTIs: Design, synthesis and biological evaluation

Drug resistance remains to be a serious problem with type I human immunodeficiency virus (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs). A series of novel boronic acid-containing diarylpyrimidine (DAPY) derivatives were designed via bioisosterism and scaffold-hopping strategies, taking advantage of the ability of a boronic acid group to form multiple hydrogen bonds. The target compounds were synthesized and evaluated for their anti-HIV activities and cytotoxicity in MT-4 cells. Compound 10j yielded the most potent activity and turned out to be a single-digit nanomolar inhibitor towards the HIV-1 IIIB [wild-type (WT) strain], L100I and K103N strains, with 50% effective concentration (EC50) values of 7.19–9.85 nmol/L. Moreover, 10j inhibited the double-mutant strain RES056 with an EC50 value of 77.9 nmol/L, which was 3.3-more potent than that of EFV (EC50 = 260 nmol/L) and comparable to that of ETR (EC50 = 32.2 nmol/L). 10j acted like classical NNRTIs with high affinity for WT HIV-1 reverse transcriptase (RT) with 50% inhibition concentration (IC50) value of 0.1837 μmol/L. Furthermore, molecular dynamics simulation indicated that 10j was proposed as a promising molecule for fighting against HIV-1 infection through inhibiting RT activity. Overall, the results demonstrated that 10j could serve as a lead molecule for further modification to address virus-drug resistance.

Covid-19 treatment: Investigation on the phytochemical constituents of Vernonia amygdalina as potential Coronavirus-2 inhibitors

The upsurge in the current cases of COVID-19 poses a major threat on human health and population all over the globe. The emergence of new infectious diseases and increase in frequency of drug resistant viruses demand effective and novel therapeutic agents. In this study, we used bioinformatics approach to investigate the possible inhibitory potentials of phytochemical constituents of Vernonia amygdalina towards coronavirus-2 major protease. Pharmacodynamics, pharmacokinetics and toxicological profiles of the compounds were also examined using the pkCSM server. All the phytochemicals showed good binding affinity to the binding pocket of PDB ID 6LU7. It was observed that veronicoside A exhibited the highest binding affinity when compared to remdesivir, hydroxy-vernolide, vernodalin, vernodalol, and vernolide. The amino acids LEU272, LEU287, GLY275, TYR237, LYS236, THR198, THR199, ARG131, and LYS5 were showed as the key residues for veronicoside A binding to human SARS-COV2 major protease. The Pharmacodynamics and pharmacokinetics results suggested that all the tested phytochemicals have significant drug likeness properties and they could be absorbed through the human intestine. Furthermore, all the tested phytochemicals are not hepatoxic and also exhibited non or relatively low toxic effects in human. Taken together, the results of this study indicated that all the tested phytochemicals are potential putative inhibitors of SARS-COV2 major protease with non or low toxicity effects. However, further experimental and clinical studies are needed to further explore their activities and validate their efficacies against COVID-19.

Differential impact of various substitutions at codon 715 in region II of HSV-1 and HCMV DNA polymerases

This study aimed at understanding the impact of different substitutions at codon 715 localized in the region II of the palm domain of herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) DNA polymerases (pol). Here, we report a new theoretical mutation V715S that confers resistance of HSV-1 to foscarnet/acyclovir (5.6- and 9.2-fold increases EC50 values compared to wild type, respectively) and of HCMV to foscarnet/ganciclovir (2.8- and 2.9-fold increases in EC50 values compared to wild type, respectively). To further analyze the importance of this amino acid, we investigated the impact of the already known mutations V715M and V715G on the replicative capacities and drug susceptibilities of both viruses as well as on the activity and drug inhibition of the DNA pol. The V715G recombinant HSV-1 mutant was resistant to foscarnet and acyclovir (3.4- and 4.6-fold EC50 increase, respectively) whereas the V715M mutant was susceptible to foscarnet and resistant to acyclovir (3.4-fold EC50 increase). The V715G recombinant HCMV mutant did not grow and the V715M mutant was resistant to foscarnet (3.7-fold EC50 increase) and susceptible to ganciclovir. Finally, we showed by three-dimensional modeling that the differential impact of these mutations on the viral replicative capacity and drug resistance profile was related to different hydrophobic local environments for V715 in the DNA pol of the two viruses. Furthermore, we hypothesize that the DNA pol of HSV-1 is more tolerant to changes at this residue compared to that of HCMV because of a more hydrophobic environment stabilizing the region.

Development and Effects of Influenza Antiviral Drugs.

Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.

Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance.

Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 "treatment for all" target. We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences. We achieved greater precision in determining the stage of infection than current incidence assays, with a 1.2% false recency rate (proportion of misclassified chronic infections) and a 262-day mean duration of recent infection (average time span of recent infection classification) from 83 recently infected and 81 chronically infected individuals. Microdrop HIV sequencing demonstrated an increased capacity to detect minority variants and linked DRMs. By screening all 93 World Health Organization surveillance DRMs, we detected 6 pretreatment drug resistance mutations with 2.6%-13.2% prevalence and cross-linked mutations. HIDA with microdrop HIV sequencing may promote global HIV real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool that can be generalized for surveillance of other pathogens.

Design and exploration of C-3 benzoic acid bioisosteres and alkyl replacements in the context of GSK3532795 (BMS-955176) that exhibit broad spectrum HIV-1 maturation inhibition

GSK3532795 (formerly BMS-955176) is a second-generation HIV-1 maturation inhibitor that has shown broad spectrum antiviral activity and preclinical PK predictive of once-daily dosing in humans. Although efficacy was confirmed in clinical trials, the observation of gastrointestinal intolerability and the emergence of drug resistant virus in a Phase 2b clinical study led to the discontinuation of GSK3532795. As part of the effort to further map the maturation inhibitor pharmacophore and provide additional structural options, the evaluation of alternates to the C-3 phenyl substituent in this chemotype was pursued. A cyclohexene carboxylic acid provided exceptional inhibition of wild-type, V370A and ΔV370 mutant viruses in addition to a suitable PK profile following oral dosing to rats. In addition, a novel spiro[3.3]hept-5-ene was designed to extend the carboxylic acid further from the triterpenoid core while reducing side chain flexibility compared to the other alkyl substituents. This modification was shown to closely emulate the C-3 benzoic acid moiety of GSK3532795 from both a potency and PK perspective, providing a non-traditional, sp3-rich bioisostere of benzene. Herein, we detail additional modifications to the C-3 position of the triterpenoid core that offer effective replacements for the benzoic acid of GSK3532795 and capture the interplay between these new C-3 elements and C-17 modifications that contribute to enhanced polymorph coverage.

Uptake of antiretroviral treatment and viral suppression among men who have sex with men and transgender women in sub-Saharan Africa in an observational cohort study: HPTN 075

ObjectivesHPTN 075 enrolled men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa. Persons in HIV care or on antiretroviral treatment (ART) were not eligible to enroll. We evaluated antiretroviral (ARV) drug use, viral suppression, and drug resistance in this cohort over a 12-month follow-up period. MethodsAssessments included 64 participants with HIV (39 MSM, 24 TGW, and one gender not specified). ARV drugs were detected using a qualitative assay. Viral load (VL) and drug resistance testing were performed using commercial assays. ResultsOver 12 months, the proportion of participants using ARV drugs increased from 28.1% to 59.4% and the proportion with VLs <400 copies/mL increased from 21.9% to 57.8%. The rate of ART failure (detection of drugs without viral suppression) was similar at screening and 12 months (12.0% and 11.1%, respectively) and was similar among MSM and TGW. Two participants developed HIV drug resistance during follow-up. ConclusionsOver 12 months, ARV drug use in the cohort more than doubled and viral suppression increased nearly threefold without a significant increase in ART failure or drug resistance. These results suggest that ART can be successfully scaled up for HIV prevention and treatment in this high-risk population.

A mathematical study on the drug resistant virus emergence with HIV/AIDS treatment cases

HIV/AIDS drug treatments, one of which is highly active anti-retroviral ther-apy (HAART), often fail by the emergence of drug resistant virus. In this paper we study a quantitative method to evaluate the chance of resistant virus gen-eration. To this end we develop a mathematical description of the possibility of the emergence of resistant virus species against drug treatments, depend-ing on the trajectories of the state variables of HIV infection dynamic model. By simulation studies of mathematical models we apply the proposed analy-sis method to HIV/AIDS drug therapies, improved gradual dosage reduction (iGDR) and structured treatment interruption (STI). Based on the analysis it can be explained the reason why STI therapy often fails. Moreover it is con-cluded that iGDR is desirable particularly by decreasing the threat of resistant virus emergence.

Video-Counseling Intervention to Address HIV Care Engagement, Mental Health, and Substance Use Challenges: A Pilot Randomized Clinical Trial for Youth and Young Adults Living with HIV

Background: Substance use and mental health are two barriers to engagement in care and antiretroviral therapy (ART) adherence among youth and young adults living with HIV (YLWH). The consequences of suboptimal adherence in YLWH are increased risk of HIV transmission and a future generation of immunodeficient adults with drug-resistant virus.Methods: The Youth to Telehealth and Texting for Engagement in Care (Y2TEC) study was a pilot randomized crossover trial that examined the feasibility and acceptability of a novel video-counseling series and accompanying text messages aimed at mental health, substance use, and HIV care engagement for YLWH. The intervention consisted of twelve 20–30-min weekly video-counseling sessions focused on identifying and addressing barriers to HIV care, mental health, and substance use challenges. Participants completed quantitative surveys at baseline, 4 months, and 8 months. Feasibility and acceptability were evaluated using prespecified benchmarks.Results: Fifty YLWH aged 18–29 years living in the San Francisco Bay Area were enrolled. Eighty-six percent and 75% of participants were retained at 4 and 8 months, respectively. A total of 455 (76%) video-counseling sessions were completed. In 82% of sessions, participants responded that they strongly agreed/agreed with this statement: “I felt heard, understood, and respected by the counselor.” In 81% of sessions, participants responded that they strongly agreed/agreed with this statement: “Overall, today's session was right for me.” At baseline, among participants reporting mental health challenges, only 10% noted having ever received mental health services, and among those who reported substance use challenges, ∼19% reported ever receiving substance use services. After 4 months of the Y2TEC intervention, participants reported slightly higher ART adherence and HIV knowledge, decreased depression and anxiety, and reduced stigma related to mental health and substance use.Conclusions: The Y2TEC intervention using video-counseling and text messaging was feasible and acceptable for YLWH. ClinicalTrials.gov ID: NCT03681145

Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses

During the last forty years we have witnessed impressive advances in the field of antiviral drug discovery culminating with the introduction of therapies able to stop human immunodeficiency virus (HIV) replication, or cure hepatitis C virus infections in people suffering from liver disease. However, there are important viral diseases without effective treatments, and the emergence of drug resistance threatens the efficacy of successful therapies used today. In this review, we discuss strategies to discover antiviral compounds specifically designed to combat drug resistance. Currently, efforts in this field are focused on targeted proteins (e.g. multi-target drug design strategies), but also on drug conformation (either improving drug positioning in the binding pocket or introducing conformational constraints), in the introduction or exploitation of new binding sites, or in strengthening interaction forces through the introduction of multiple hydrogen bonds, covalent binding, halogen bonds, additional van der Waals forces or multivalent binding. Among the new developments, proteolysis targeting chimeras (PROTACs) have emerged as a valid approach taking advantage of intracellular mechanisms involving protein degradation by the ubiquitin-proteasome system. Finally, several molecules targeting host factors (e.g. human dihydroorotate dehydrogenase and DEAD-box polypeptide 3) have been identified as broad-spectrum antiviral compounds. Implementation of herein described medicinal chemistry strategies are expected to contribute to the discovery of new drugs effective against current and future threats due to emerging and re-emerging viral pandemics.

Nanodiamonds: A Versatile Drug-Delivery System in the Recent Therapeutics Scenario

Nanodiamonds (ND) belong to the nano-carbon family, which involves several synthesis, post-synthesis methods, and other modifications for ND preparation. NDs have played vital role both inside and outside of medicine in recent years. The study of NDs has stated in early 1960s, NDs are smaller particles with a size of about 4-5 nm with confined size distribution, large-scale synthesis at lower costs relying on the carbon explosives ignition, apparent surface functional design along with bio-conjugation and extreme biocompatibility. It has been predicted that the ND's magnetic characteristics will contribute to the up-growth of various therapeutic promoters for delivery vehicles, diagnostic probes, gene therapy, tissue scaffolds, anti-bacterial and anti-viral treatments, and devices like nano-robots. Furthermore, the wide applications of biotechnology have displayed the potential usage of NDs in certain bioanalytical needs like fluorescent bio labeling through fluorescent and protein purification of proteins. In this current review, the determination of ND's design, property, classes, constancy, organization, surface modification, biocompatibility, and its applications in the biomedical field have penned. The usage of ND as anti-neoplastic agents and in other health related formulations have displayed exceptional results for future growth. Additionally, NDs provide other functionalities such as production of biodegradable surgical devices of bone, the assassination of drug resistant microbes and viruses, tissue engineering scaffolds, and aids in the delivery of genetic matter into the nucleus of cells.

Relationship Between Drug Resistance and Death in HIV-Infected Patients Receiving Antiretroviral Therapy - 7 PLADs, China, 2010-2019.

What is already known about this topic?With increasing coverage of antiretroviral therapy (ART) for HIV-infected patients, more and more attention has been paid to the impact of HIV drug resistance on death in those patients in China.What is added by this report?Among HIV-infected patients receiving ART, the risk of death is higher in patients with HIV drug resistance [adjusted odds ratio (AOR)=4.25, 95% confidence interval (CI): 2.10–8.62], with viral load ≥1,000 copies/mL but drug resistance untested (AOR=4.65, 95% CI: 1.74–12.39), and with neither viral load nor drug resistance being tested (AOR=17.52, 95% CI: 8.73–35.19) when compared with drug-sensitive patients.What are the implications for public health practice?It is important to strengthen drug resistance monitoring and prevention in HIV-infected patients. While performing ART for HIV-infected patients, viral load testing and drug resistance testing should be carried out routinely and promptly.