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1.
Molecules ; 28(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37687159

ABSTRACT

The use of protease inhibitors in human immunodeficiency virus type 1 (HIV-1) treatment is limited by adverse effects, including metabolic complications. To address these challenges, efforts are underway in the pursuit of more potent and less toxic HIV-1 protease inhibitors. Repurposing existing drugs offers a promising avenue to expedite the drug discovery process, saving both time and costs compared to conventional de novo drug development. This study screened FDA-approved and investigational drugs in the DrugBank database for their potential as HIV-1 protease inhibitors. Molecular docking studies and cell-based assays, including anti-HIV-1 in vitro assays and XTT cell viability tests, were conducted to evaluate their efficacy. The study findings revealed that CBR003PS, an antibiotic currently in clinical use, and CBR013PS, an investigational drug for treating endometriosis and uterine fibroids, exhibited significant binding affinity to the HIV-1 protease with high stability. Their EC50 values, measured at 100% cell viability, were 9.4 nM and 36.6 nM, respectively. Furthermore, cell-based assays demonstrated that these two compounds showed promising results, with therapeutic indexes higher than 32. In summary, based on their favorable therapeutic indexes, CBR003PS and CBR013PS show potential for repurposing as HIV-1 protease inhibitors.


Subject(s)
HIV-1 , Protease Inhibitors , Female , Humans , Protease Inhibitors/pharmacology , Molecular Docking Simulation , Enzyme Therapy , Anti-Bacterial Agents , Drugs, Investigational
2.
iScience ; 26(8): 107245, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37520737

ABSTRACT

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is recommended in revascularization guidelines for intermediate lesions. However, recent studies comparing FFR-guided PCI with non-physiology-guided revascularization have reported conflicting results. PubMed and Embase were searched for studies comparing FFR-guided PCI with non-physiology-guided revascularization strategies (angiography-guided, intracoronary imaging-guided, coronary artery bypass grafting). Data were pooled by meta-analysis using random-effects model. 26 studies enrolling 78,897 patients were included. FFR-guided PCI as compared to non-physiology-guided coronary revascularization had lower risk of all-cause mortality (odds ratio [OR] 0.79 95% confidence interval [CI] 0.64-0.99, I2 = 53%) and myocardial infarction (MI) (OR 0.74 95% CI 0.59-0.93, I2 = 44.7%). However, no differences between groups were found in terms of major adverse cardiac events (MACEs) (OR 0.86 95% CI 0.72-1.03, I2 = 72.3%) and repeat revascularization (OR 1 95% CI 0.82-1.20, I2 = 43.2%). Among patients with coronary artery disease (CAD), FFR-guided PCI as compared to non-physiology-guided revascularization was associated with a lower risk of all-cause mortality and MI.

3.
J Med Act Plants ; 12(1): 1-17, 2023 Mar.
Article in English | MEDLINE | ID: mdl-38234988

ABSTRACT

The search for alternative naturally occurring antimicrobial agents will always continue, especially when emerging diseases like COVID-19 provide an urgency to identify and develop safe and effective ways to prevent or treat these infections. The purpose of this study was to evaluate the potential antimicrobial activity as well as antioxidant properties of commercial samples from four traditional medicinal plants used in Central America: Theobroma cacao, Bourreria huanita, Eriobotrya japonica, and Elettaria cardamomum. Ethanolic extracts were prepared from commercial products derived from the seeds or flowers of these plants. Total phenolics and antioxidant activity were assessed using commercial kits. The cytotoxicity and antiviral activity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) were evaluated using the XTT colorimetric assay and a SARS-CoV-2 delta pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were used to calculate the therapeutic index (TI). Additionally, the antibacterial activity against Escherichia coli and Staphylococcus epidermidis was tested using a spectrophotometric method. The extracts showed total phenolics in the range of 0.06 to 1.85 nM/µL catechin equivalents, with T. cacao bean extract showing the highest content. The antioxidant activity showed values between 0.02 and 0.44 mM Trolox equivalents. T. cacao bean extract showed the highest antioxidant activity. Most plant extracts showed zero to moderate selective antiviral activity; however, one T. cacao beans sample showed excellent antiviral activity against SARS-CoV-2 with a TI value of 30.3, and one sample of E. japonica showed selective antiviral activity with a TI value of 18.7. Significant inhibition of E. coli and S. epidermidis by an E. japonica ethanolic extract (p<0.001) was observed using a spectrophotometric method that monitors bacterial growth over time. Additionally, ethanolic extracts of E. cardamomum showed significant inhibition of S. epidermidis growth (p<0.001). The results warrant further investigation of the antimicrobial and antioxidant properties of these plant extracts.

4.
ACS Omega ; 7(33): 28779-28789, 2022 Aug 23.
Article in English | MEDLINE | ID: mdl-35991504

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Several variants of SARS-CoV-2 have emerged worldwide. These variants show different transmissibility infectivity due to mutations in the viral spike (S) glycoprotein that interacts with the human angiotensin-converting enzyme 2 (hACE2) receptor and facilitates viral entry into target cells. Despite the effective SARS-CoV-2 vaccines, we still need to identify selective antivirals, and the S glycoprotein is a key target to neutralize the virus. We hypothesize that small molecules could disrupt the interaction of S glycoprotein with hACE2 and inhibit viral entry. We analyzed the S glycoprotein-hACE2 complex structure (PDB: 7DF4) and created models for different viral variants using visual molecular dynamics (VMD) and molecular operating environment (MOE) programs. Moreover, we started the hits search by performing structure-based molecular docking virtual screening of commercially available small molecules against S glycoprotein models using OEDocking FRED-4.0.0.0 software. The FRED-4.0.0.0 Chemguass4 scoring function was used to rank the small molecules based on their affinities. The best candidate compounds were purchased and tested using a standard SARS-CoV-2 pseudotyped cell-based bioassay to investigate their antiviral activity. Three of these compounds, alone or in combination, showed antiviral selectivity. These small molecules may lead to an effective antiviral treatment or serve as probes to better understand the biology of SARS-CoV-2.

5.
PLoS One ; 17(1): e0261775, 2022.
Article in English | MEDLINE | ID: mdl-35051209

ABSTRACT

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT's preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24-45 years. In the open label period, all participants (n = 7) received single dose of PC-6500. In the randomized period, participants (n = 13) were instructed to self-administer 14 doses of PC-6500 or its matching CG placebo (PC-535) once daily for 14 days. The primary outcomes were safety and PK after single dose, and then after 14 days of dosing. Exploratory outcomes were GRFT concentrations in cervicovaginal fluids, PD, inflammatory mediators and gene expression in ectocervical biopsies. This trial is registered with ClinicalTrials.gov, number NCT02875119. No significant adverse events were recorded in clinical or laboratory results or histopathological evaluations in cervicovaginal mucosa, and no anti-drug (GRFT) antibodies were detected in serum. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Decreased levels of proinflammatory chemokines (CXCL8, CCL5 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in cervicovaginal lavage samples inhibited HIV and HPV, respectively, in vitro in a dose-dependent fashion. These data suggest GRFT formulated in a CG gel is a safe and promising on-demand multipurpose prevention technology product that warrants further investigation.


Subject(s)
Carrageenan/administration & dosage , HIV Infections/prevention & control , Papillomavirus Infections/prevention & control , Plant Lectins/administration & dosage , Pre-Exposure Prophylaxis , Vaginal Creams, Foams, and Jellies/administration & dosage , Administration, Intravaginal , Adolescent , Adult , Double-Blind Method , Female , HIV-1 , Humans , Middle Aged , Papillomaviridae
6.
S Afr J Bot ; 146: 735-739, 2022 May.
Article in English | MEDLINE | ID: mdl-34955582

ABSTRACT

Plant-based compounds with antiviral properties against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified in Aframomum melegueta through computational models. The seed extract have been traditionally used to treat different illnesses. In this study, ethanolic extracts were prepared for six commercial samples of A. melegueta seeds. Antiviral activity was tested using the XTT cytotoxicity assay and cell-based SARS-CoV-1 and 2 pseudoviral models. The presence of gingerols and other non-volatile components in the seed extracts was determined using an Agilent 1290 UPLC/DAD in tandem with an Agilent 6546 QTOF-MS. Our results showed selective antiviral activity with TI values as high as 13.1. Fifteen gingerols were identified by chromatographic analysis, with 6-gingerol being the dominant component in each seed extract. A combination of 6-gingerol with techtochrysin, previously identified in computational models as a potential active ingredient against SARS-CoV-2, demonstrated additive antiviral activity with CI values between 0.8715 and 0.9426. We confirmed the antiviral activity of A. melegueta predicted through computational models and identified a different compound, 6-gingerol, as a potential active ingredient.

7.
J Med Act Plants ; 11(1): 1-21, 2022 Mar.
Article in English | MEDLINE | ID: mdl-38234457

ABSTRACT

Kigelia africana and Garcinia kola are two West African medicinal plants traditionally used to treat or alleviate various medical conditions such as skin ailments, respiratory disorders, and digestive problems. Phytochemical analyses indicated the presence of bioactive constituents, including flavonoids and phenolic acids, suggesting that the extracts of these two plants can interfere with reactive oxygen species-induced oxidative stress, inflammation, and microbial growth. This paper reviews the biochemical properties and the antioxidant, anti-inflammatory, and antibacterial activities of these two relevant West African medicinal plants.

8.
Mar Drugs ; 19(8)2021 Jul 26.
Article in English | MEDLINE | ID: mdl-34436255

ABSTRACT

Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC50/EC50) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC50 between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Carrageenan/pharmacology , Plant Lectins/pharmacology , SARS-CoV-2/drug effects , Severe acute respiratory syndrome-related coronavirus/drug effects , COVID-19/virology , Drug Synergism , HeLa Cells , Humans , Models, Biological , Polysaccharides/pharmacology , COVID-19 Drug Treatment
9.
IUCrdata ; 6(Pt 1): x201663, 2021 Jan.
Article in English | MEDLINE | ID: mdl-36340467

ABSTRACT

The title compound, C24H24FNO3S, is an inter-mediate in the synthesis of fluorine containing iso-quinoline alkaloids, which crystallizes in the triclinic space group P with one mol-ecule in the asymmetric unit. The structure presents a racemic mixture of enanti-omers. The C-S-C-C torsion angle between the benzene ring system and the sulfonyl benzene ring is -178.5 (1)°. In the crystal, N-H⋯O hydrogen bonds between neighbouring mol-ecules form chains of mol-ecules along the a-axis direction.

10.
J Mol Model ; 26(11): 319, 2020 Oct 26.
Article in English | MEDLINE | ID: mdl-33104901

ABSTRACT

Halogen bonding is a noncovalent interaction that has attracted great attention because of its importance in several areas, such as photonics, nonlinear optics, pharmaceutical products, supramolecular engineering, biochemistry, protein-ligand complexes, and polymer interactions. In this context, we describe the synthesis, molecular structure, supramolecular arrangement, and theoretical calculations of five dibromonitrobenzene derivatives, which present different halogen atoms substituted. The solid-state characterization was carried out by X-ray diffraction with the contribution of Hirshfeld surfaces for analysis of molecular interactions. The frontier molecular orbital, molecular electrostatic potential, and quantum theory of atoms in molecules were carried out at the M06-2X/6-311+G(d,p) level of theory. Those observed halogen interactions indicate the crystalline solid-state stabilization for the dibromonitrobenzene derivatives.

11.
Am J Infect Control ; 48(8): 948-950, 2020 08.
Article in English | MEDLINE | ID: mdl-32046882

ABSTRACT

This study utilized fluorescent particle powder to investigate 2 potential sources of sterile field contamination in the operating room (OR): forced-air warming blankets and OR light manipulation. In part 1, sterile draping for knee replacement surgery was performed on a mannequin in a sterile OR, comparing field contamination with the forced-air warming on versus off during draping. In part 2, OR lights coated with fluorescent powder were manipulated over a sterile field. Proper operation of these devices may reduce the particle burden on the surgical field.


Subject(s)
Arthroplasty, Replacement, Knee , Hypothermia , Orthopedic Procedures , Humans , Operating Rooms , Powders
12.
J Knee Surg ; 33(4): 399-409, 2020 Apr.
Article in English | MEDLINE | ID: mdl-30708384

ABSTRACT

The purpose of this study was to compare the health-related quality of life (HRQoL) before and after successful total knee arthroplasty (TKA) across World Health Organization (WHO) body mass index (BMI) classifications. Through an institutional registry, patients with end-stage knee osteoarthritis who received elective primary unilateral TKA were identified and categorized based on WHO BMI classification. Age, gender, laterality, year of surgery, and Charlson-Deyo comorbidity index were recorded. The primary outcome was the EQ-5D-3L index and visual analog scale (VAS) at 2 years postoperatively. Inferential statistics and regression analyses were performed to determine associations between BMI classification and HRQoL. EQ-5D-3L index and VAS scores were significantly different across BMI classes, with higher scores in patients with lower BMI at baseline and at 2 years. There was no difference observed for the 2-year change in EQ-VAS scores between groups, but there was a statistically greater increase in index scores for more obese patients. In the regression analyses, there were statistically significant negative effect estimates for EQ-VAS and index scores associated with increasing BMI class, particularly for class III obesity. Higher BMI classification is independently associated with lower HRQoL scores 2 years after uncomplicated primary TKA, although obese patients experienced greater benefits in EQ-5D index scores following TKA. These results detail the relationship between BMI and HRQoL following TKA and suggest that preoperative weight loss may lead to improved outcomes following TKA, but also that obesity, alone, should not be a contraindication to TKA.


Subject(s)
Arthroplasty, Replacement, Knee , Obesity/complications , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/surgery , Quality of Life , Aged , Body Mass Index , Female , Humans , Male , Middle Aged , Registries , Visual Analog Scale , Weight Loss
15.
J Arthroplasty ; 34(4): 693-699, 2019 04.
Article in English | MEDLINE | ID: mdl-30616976

ABSTRACT

BACKGROUND: Obesity is a risk factor for acetabular component malposition when total hip arthroplasty is performed with manual techniques. The utility of imageless navigation in obese patients remains unknown. This study compared the accuracy and precision of imageless navigation for component orientation between obese and nonobese patients. METHODS: A total of 459 total hip arthroplasties performed for osteoarthritis using imageless navigation were reviewed from a single surgeon's institutional review board-approved database. Einzel-Bild-Roentgen Analyse determined component orientation on 6-week postoperative anteroposterior radiographs. Mean orientation error (accuracy) and precision were compared between obese (body mass index ≥ 30 kg/m2) and nonobese patients. Regression analysis evaluated the influence of obesity on component position. RESULTS: The difference in mean inclination and anteversion between obese and nonobese groups was 1.1° (43.0° ± 3.5°; range, 35.8°-57.8° vs 41.9° ± 4.4°; range, 33.0°-57.1° and 24.9° ± 6.3°; range, 14.2°-44.3° vs 23.8° ± 6.6°; range, 7.0°-38.6°, respectively). Inclination precision was better for nonobese patients. No difference in inclination accuracy or anteversion accuracy or precision was detected between groups. And 83% of components were placed within the target range. There was no relationship between obesity (dichotomized) and component placement outside the target ranges for inclination, anteversion, or both. As a continuous variable, increased body mass index correlated with higher odds of inclination outside the target zone (odds ratio, 1.06; P = .001). CONCLUSION: Using imageless navigation, inclination orientation was less precise for obese patients, but the observed difference is likely not clinically relevant. Accurate superficial registration of landmarks in obese patients is achievable, and the use of imageless navigation similarly improves acetabular component positioning in obese and nonobese patients. LEVEL OF EVIDENCE: Therapeutic Level IV.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/statistics & numerical data , Obesity , Surgery, Computer-Assisted/statistics & numerical data , Acetabulum/diagnostic imaging , Aged , Arthroplasty, Replacement, Hip/methods , Body Mass Index , Female , Hip Prosthesis , Humans , Male , Middle Aged , Postoperative Period , Radiography , Retrospective Studies , Risk Factors , Surgery, Computer-Assisted/methods , Treatment Outcome
17.
AME Case Rep ; 2: 6, 2018.
Article in English | MEDLINE | ID: mdl-30264002

ABSTRACT

Rectal cancer is one of the commonest human malignancies. Treatment of this serious disease conventionally involves resection with/without anastomosis. Anastomotic site stenosis is a serious complication of rectal resection for which treatment is still evolving. We report a male patient treated with minimally invasive abdominal and anal approach for stenosis after initial transanal total mesorectal excision (TaTME) for rectal cancer. Surgeons are encouraged to put this technique in their mind while treating similar cases.

18.
J Laparoendosc Adv Surg Tech A ; 28(12): 1476-1482, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30222514

ABSTRACT

BACKGROUND: Rectal cancer is now an increasing problem in both developed and developing countries. In the last 7 years, minimally invasive surgery for this disease has entered a new era of transanal resection with/without laparoscopic assistance. MATERIALS AND METHODS: We present here a prospective study done in Egypt (probably the earliest experience) and Spain on the feasibility of hybrid NOTES in rectal cancer. RESULTS: From September 2015 till November 2017, 18 cases underwent transanal total mesorectal excision with no detected mortality and with morbidities in 44% of cases, from which 5 were class III on Clavien-Dindo scale requiring intervention. Good quality total mesorectal excision was obtained in more than three quarters of our patients. CONCLUSIONS: In our experience, the technique was technically demanding with a long learning curve; however, the short term results were very good in alliance with other few similar reports.


Subject(s)
Rectal Neoplasms/surgery , Transanal Endoscopic Surgery/methods , Adult , Aged , Aged, 80 and over , Egypt , Feasibility Studies , Female , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Male , Middle Aged , Pilot Projects , Postoperative Complications/epidemiology , Prospective Studies , Rectum/pathology , Rectum/surgery , Spain , Transanal Endoscopic Surgery/adverse effects , Treatment Outcome
19.
Nat Commun ; 9(1): 3881, 2018 09 24.
Article in English | MEDLINE | ID: mdl-30250170

ABSTRACT

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Moreover, on-demand products are currently missing from the PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. When combined with carrageenan (CG), GRFT has strong activity against herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV) in vitro and in vivo. Here, we report that GRFT/CG in a freeze-dried fast dissolving insert (FDI) formulation for on-demand use protects rhesus macaques from a high dose vaginal SHIV SF162P3 challenge 4 h after FDI insertion. Furthermore, the GRFT/CG FDI also protects mice vaginally against HSV-2 and HPV pseudovirus. As a safe, potent, broad-spectrum, on-demand non-antiretroviral product, the GRFT/CG FDI warrants clinical development.


Subject(s)
Acquired Immunodeficiency Syndrome/prevention & control , Antiviral Agents/therapeutic use , Carrageenan/therapeutic use , Herpes Genitalis/prevention & control , Papillomavirus Infections/prevention & control , Plant Lectins/therapeutic use , Administration, Intravaginal , Animals , Antiviral Agents/chemistry , Carrageenan/chemistry , Disease Models, Animal , Drug Compounding/methods , Drug Evaluation, Preclinical , Female , Freeze Drying , Herpes Genitalis/virology , Herpesvirus 2, Human/pathogenicity , Humans , Macaca mulatta , Male , Papillomavirus Infections/virology , Plant Lectins/chemistry , Plant Lectins/genetics , Plant Lectins/isolation & purification , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Pre-Exposure Prophylaxis/methods , Simian Acquired Immunodeficiency Syndrome/prevention & control , Simian Immunodeficiency Virus/pathogenicity , Nicotiana/genetics , Nicotiana/metabolism , Treatment Outcome , Vagina/virology
20.
Drug Deliv Transl Res ; 7(6): 859-866, 2017 12.
Article in English | MEDLINE | ID: mdl-28812250

ABSTRACT

We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC50 values between 20 and 110 µM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.


Subject(s)
Anti-Retroviral Agents/administration & dosage , HIV-1/drug effects , Pyridines/administration & dosage , Urea/analogs & derivatives , Zinc Acetate/administration & dosage , Anti-Retroviral Agents/pharmacology , Drug Resistance, Viral/drug effects , Drug Therapy, Combination , HIV-1/genetics , Humans , Microbial Sensitivity Tests , Pyridines/pharmacology , Urea/administration & dosage , Urea/pharmacology , Zinc Acetate/pharmacology
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