Microwave assisted synthesis of 2-amino-4-chloro-pyrimidine derivatives: Anticancer and computational study on potential inhibitory action against COVID-19.

We report microwave synthesis of seven unique pyrimidine anchored derivatives (1-7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1-7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1-7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively. Molecular docking was performed for derivatives (1-7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of -8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1-7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of -0.03 and -0.018, respectively and absence of AMES toxicity.

Hydrothermal Synthesis of ß-Nb2ZnO6 Nanoparticles for Photocatalytic Degradation of Methyl Orange and Cytotoxicity Study.

ß-Nb2ZnO6 nanoparticles were synthesized by a hydrothermal process and calcined at two temperatures, 500 °C and 700 °C, and assigned as A and B, respectively. X-ray diffraction, together with transmission electron microscopy, revealed that the ß-Nb2ZnO6 nanoparticles calcined at 700 °C (B) were more crystalline than the ß-Nb2ZnO6 calcined at 500 °C (A) with both types of nanoparticles having an average size of approximately 100 nm. The physiochemical, photocatalytic, and cytotoxic activities of both types of ß-Nb2ZnO6 nanoparticles (A and B) were examined. Interestingly, the photodegradation of methyl orange, used as a standard for environmental pollutants, was faster in the presence of the ß-Nb2ZnO6 nanoparticles calcined at 500 °C (A) than in the presence of those calcined at 700 °C (B). Moreover, the cytotoxicity was evaluated against different types of cancer cells and the results indicated that both types of ß-Nb2ZnO6 nanoparticles (A and B) exhibited high cytotoxicity against MCF-7 and HCT116 cells but low cytotoxicity against HeLa cells after 24 and 48 h of treatment. Overall, both products expressed similar EC50 values on tested cell lines and high cytotoxicity after 72 h of treatment. As a photocatalyst, ß-Nb2ZnO6 nanoparticles (A) could be utilized in different applications including the purification of the environment and water from specific pollutants. Further biological studies are required to determine the other potential impacts of utilizing ß-Nb2ZnO6 nanoparticles in the biomedical application field.

Quality variation and standardization of black pepper (Piper nigrum): A comparative geographical evaluation based on instrumental and metabolomics analysis.

Black pepper (Piper nigrum; BP), known as the 'king of spices', imported from various countries is widely available in Saudi Arabian markets, as its demand as a food as well as a medicine for minor ailments is increasing in the country. However, there is a lack of appropriate information regarding these samples in terms of quality variation and standardization. We thus aimed to evaluate the quality and standardize the BP sample with respect to its physicochemical characters, active principle variation [i.e. piperine (PPN)], toxicity, and biological activity. The main focus is to validate whether any difference exists in the quality and quantity of active principle in these samples. For this purpose, physicochemical (chemical tests and ash values) and instrumental analyses [accelerated solvent extraction (ASE), ultra-high-pressure liquid chromatography (UHPLC)-diode array detector, infrared (IR), nuclear magnetic resonance (NMR), and inductively coupled plasma-MS (ICP-MS)] and biological evaluation {in vitro antioxidant activity [2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] and cytotoxicity assay} were performed. An extract yield (g) with %recovery of 2.26 ± 4.24 (11.3) was obtained for the Vietnamese sample, using a fast and rapid method of extraction (ASE). These values were 1.22 ± 2.64 (6.1) and 0.75 ± 1.69 (3.75) for the Pakistani and Indian samples. Physicochemical tests revealed the presence of flavonoids and phenolic compounds in all samples; however, in the Vietnamese sample a low amount of total, acid-insoluble, and high water-soluble ash value was noted. IR and NMR was applied to further standardize the samples. Results of ICP-MS analysis showed a high amount of macronutrients and micronutrients in the samples tested while UHPLC analysis revealed a high amount of PPN (ng/mL) in the Pakistani sample (1,362,614.09); these values were 1,051,848.04 and 768,512.81 for the Vietnamese and Indian samples, respectively. In vitro antioxidant and cytotoxicity activities revealed higher potential for the Vietnamese sample. The samples were properly standardized and effectively differentiated in terms of quality and biological activities using a fast and reliable method, however it certainly does not mean that a particular geographical region is more better or productive in terms of herbal products.

Synthesis and characterization of cadmium-bismuth microspheres for the catalytic and photocatalytic degradation of organic pollutants, with antibacterial, antioxidant and cytotoxicity assay.

Cadmium-Bismuth microspheres (CdS-Bi2S3) were prepared by facile solvothermal method with polyvinylpyrrolidone (PVP) employed to control the morphology of CdS-Bi2S3. The product was characterized using X-ray diffraction (XRD), scanning electron microscope (SEM), diffuse reflectance UV-vis spectrophotometer and surface area of CdS-Bi2S3 was determined by BET analyzer. It was observed that CdS-Bi2S3 spheres exhibited good catalytic activity for the reduction of 4-nitrophenol. The photocatalytic application of CdS-Bi2S3 was evaluated for the photocatalytic degradation of environmental pollutants such as methyl orange, and methyl green under UV-visible light irradiation and it demonstrated good photocatalytic activity. Furthermore, we studied the antioxidant activity of CdS-Bi2S3 and it was observed that CdS-Bi2S3 showed antioxidant activity at all tested concentrations (5, 3 and 1 mg/mL). Antimicrobial activity of CdS-Bi2S3 microspheres was also studied for microbial control and the tested nanospheres proved to be exceptional antibacterial agent against tested Gram-positive and Gram-negative bacteria. CdS-Bi2S3 microspheres also exhibited significant cytotoxicity activity against HCT 116 (Human colon colorectal tumor) cell line. Our results indicate that CdS-Bi2S3 is good photocatalyst with several biological activities. The effective preparation method of CdS-Bi2S3 could be useful to design and fabricate the novel photocatalyst which may have several applications in the field of catalysis and in the medicine.

SPIONs/3D SiSBA-16 based Multifunctional Nanoformulation for target specific cisplatin release in colon and cervical cancer cell lines.

Multifunctional nanomaterials can be used for dual applications: drug delivery as well as in bioimaging. In current study, we investigated potential use of silica based supports; 3D cage type SiSBA-16 (S-16), monodispersed hydrophilic spherical silica (HYPS) and mesocellular foam (MSU-F) for cisplatin (Cp) delivery. To obtain magnetic resonance characteristics, 10 wt% iron oxide was loaded through enforced adsorption technique. For pH stimuli responsive release of Cp, 10 wt%SPIONs/S-16 was functionalized with 3-(Aminopropyl)triethoxysilane (A) and poly acrylic acid (PAA) termed as 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp. By TEM analysis, the average diameter of the SPIONs was found to range between 10-60 nm. VSM analysis showed saturation magnetization over S-16, HYPS and MSU-F were in the following order: 10 wt%SPIONs/HYPS (4.08 emug-1) > 10 wt%SPIONs /S-16 (2.39 emug-1) > 10 wt%SPIONs/MSU-F (0.23 emug-1). Cp release study using dialysis membrane in PBS solution over 10 wt%SPIONs/S-16 nanoformulations showed highest cumulative release (65%) than 10 wt%SPIONs/MSU-F-A-Cp (63%), 10 wt%SPIONs/HYPS-A-Cp (58%), and Cp-F127/S-16 (53%), respectively. 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp were evaluated for in vitro target anticancer efficiency in human cancer cell lines (colon cancer (HCT 116), cervical cancer (HeLa)) and normal cells (Human embryonic kidney cells (HEK293) using MTT and DAPI staining. 10 wt%SPIONs/S-16-A-Cp treated Hela and HCT116 cancerous cell lines showed significant control of cell growth, apoptotic activity and less cytotoxic effect as compared to Cp and 10 wt%SPIONs/S-16. Target specific Cp release in the cells shows that 10 wt%SPIONs/S-16-A-Cp can be easily upgraded for magnetic resonance imaging capability.

Cisplatin-functionalized three-dimensional magnetic SBA-16 for treating breast cancer cells (MCF-7).

The engineering of multifunctional therapeutics in an integrated single platform is demonstrated using three-dimensional SBA-16 (S-16). 10 wt% iron oxide nanoparticles (Fe) were loaded into the cage type of cubic pores through enforced adsorption technique. Fe/S-16 is then functionalized with amine-based silane (A), polyacrylic acid (P) and cisplatin (Cp). The physicochemical textural analysis showed the formation of nano metal oxide distributions at pore walls of S-16 with magnetization of 2.39 emu/g. S-16 based nanoformulations showed high percentage of Cp adsorption (90%) and percentage cumulative release (60%). in vitro study of Fe/S-16-A-Cp showed high toxicity against breast cancer cell line MCF-7 and normal cell line Human foreskin fibroblast (HFF-1) compared to Fe/S-16 indicating cisplatin profusion inside the cells than free cisplatin. While skin fibroblast seems to be resistant to Fe/S-16-AP-Cp with very high LC50 in compare to MCF-7. This indicates the unrelease of cisplatin in skin fibroblast after Fe/S-16-AP-Cp treatment due to effective encapsulation inside the cubic pores and core blockage due to pH-sensitive polyacrylic acid. Also, these treatments resulted in morphological changes in the cells such as DNA condensation and nuclear fragmentation.

Role of Lipid Rafts in Hematopoietic Stem Cells Homing, Mobilization, Hibernation, and Differentiation.

Hematopoietic stem cells (HSCs) are multipotent, self-renewing cells that can differentiate into myeloid or lymphoid cells. The mobilization and differentiation processes are affected by the external environment, such as extracellular matrix and soluble molecules in the niche, where the lipid rafts (LRs) of the HSCs act as the receptors and control platforms for these effectors. LRs are membrane microdomains that are enriched in cholesterol, sphingolipid, and proteins. They are involved in diverse cellular processes including morphogenesis, cytokinesis, signaling, endocytic events, and response to the environment. They are also involved in different types of diseases, such as cancer, Alzheimer's, and prion disease. LR clustering and disruption contribute directly to the differentiation, homing, hibernation, or mobilization of HSCs. Thus, characterization of LR integrity may provide a promising approach to controlling the fate of stem cells for clinical applications. In this review, we show the critical role of LR modification (clustering, disruption, protein incorporation, and signal responding) in deciding the fate of HSCs, under the effect of soluble cytokines such as stem cell factor (SCF), transforming growth factor- ß (TGF-ß), hematopoietic-specific phospholipase Cß2 (PLC-ß2), and granulocyte colony-stimulating factor (G-CSF).

Targeted delivery of poly (methyl methacrylate) particles in colon cancer cells selectively attenuates cancer cell proliferation.

Poly (methyl methacrylate) (PMMA) is basically biocompatible polyester with high resistance to chemical hydrolysis, and high drug permeability and the most important characteristics of PMMA is that it does not produce any toxicity. There is not much information about PMMA action on the colon cancer cells. In the present study, we have synthesized PMMA nanoparticles. The distribution pattern of PMMA particles was analysed by Zeta sizer and the size of the particles was calculated by using quasi elastic light scattering (QELS). The surface structure and the morphology of PMMA were characterized by transmission electron microscope (TEM) and scanning electron microscope (SEM), respectively. We have also analysed their effects on cancerous cells (human colorectal carcinoma cells, HCT-116) and normal, healthy cells (human embryonic kidney cells, HEK-293) by using morphometric, MTT, DAPI and wound healing methods. We report that PMMA particles inhibited the cancer cell viability in a dose-dependent manner. The lower dose (1.0 µg/ml) showed a moderate decrease in cancer cell viability, whereas higher dosages (2.5 µg/ml, 5.0 µg/mL and 7.5 µg/mL) showed steadily decrease in the cancer cell viability. We also report that PMMA is highly selective to cancerous cells (HCT-116), as we did not find any action on the normal healthy cells (HEK-293). In conclusion, our results suggest PMMA particles are potential biomaterials to be used in the treatment of colon cancer.

Cisplatin delivery, anticancer and antibacterial properties of Fe/SBA-16/ZIF-8 nanocomposite.

Nanoformulation involving biocompatible MOFs and magnetic nanocarriers is an emerging multifunctional platform for drug delivery and tumor imaging in targeted cancer therapeutics. In this study, a nanocomposite has been developed comprising Fe/SBA-16 and ZIF-8 (Fe/S-16/ZIF-8) through ultrasonication. The drug delivery of cisplatin was studied using an automated diffusion cell system equipped with a flow type Franz cell. The anticancer activity of Fe/S-16/ZIF-8 was studied in vitro in MCF-7, HeLa cells and Human Foreskin Fibroblast (HFF-1) cells. XRD and d-spacing measurements of Fe/S-16/ZIF-8 using TEM revealed the presence of cubic-structured Fe3O4, γ-Fe2O4 (magnetite), and α-FeOOH (goethite) over an SBA-16/ZIF-8 nanocomposite. The composite showed a surface area of 365 m2 g-1, a pore size of 8.3 nm and a pore volume of 0.33 cm3 g-1. VSM analysis of Fe/S-16/ZIF-8 showed that it possessed paramagnetic behavior with a saturated magnetization value of 2.39 emu g-1. The Fe2+/Fe3+ coordination environment was characterized using diffuse reflectance spectroscopy. The cisplatin drug delivery study clearly showed the synergistic effects present in Fe/S-16/ZIF-8 with over 75% of cisplatin release as compared to that of Fe/S-16 and ZIF-8, which showed 56% and 7.5%, respectively. The morphology analysis of CP/Fe/SBA-16/ZIF-8 using TEM showed an effective transit of nanoparticles into MCF-7 cells. The lethal concentration (LC50) of Fe/SBA-16/ZIF-8 for MCF-7 and HeLa cells is 0.119 mg mL-1 and 0.028 mg mL-1 at 24 h, respectively. For HFF-1 cells, the LC50 is 0.016 mg mL-1. The antibiofilm activity of Fe/SBA-16/ZIF-8 was investigated against biofilm-forming strains of drug resistant P. aeruginosa and MRSA by a microtiter tissue culture plate assay. Overall, nanosized ZIF-8 with a bioactive alkaloid imidazole inside the 3D cage type of SBA-16 pores is found to exhibit both anticancer and antibacterial properties. A Fe/S-16/ZIF-8 composite could be effectively used as a drug and drug delivery system against cancer and promote antibacterial activity.

Isolation, Culture, and Functional Characterization of Human Embryonic Stem Cells: Current Trends and Challenges.

Human embryonic stem cells (hESCs) hold great potential for the treatment of various degenerative diseases. Pluripotent hESCs have a great ability to undergo unlimited self-renewal in culture and to differentiate into all cell types in the body. The journey of hESC research is not that smooth, as it has faced several challenges which are limited to not only tumor formation and immunorejection but also social, ethical, and political aspects. The isolation of hESCs from the human embryo is considered highly objectionable as it requires the destruction of the human embryo. The issue was debated and discussed in both public and government platforms, which led to banning of hESC research in many countries around the world. The banning has negatively affected the progress of hESC research as many federal governments around the world stopped research funding. Afterward, some countries lifted the ban and allowed the funding in hESC research, but the damage has already been done on the progress of research. Under these unfavorable conditions, still some progress was made to isolate, culture, and characterize hESCs using different strategies. In this review, we have summarized various strategies used to successfully isolate, culture, and characterize hESCs. Finally, hESCs hold a great promise for clinical applications with proper strategies to minimize the teratoma formation and immunorejection and better cell transplantation strategies.

Preparation, formation mechanism, photocatalytic, cytotoxicity and antioxidant activity of sodium niobate nanocubes.

A hydrothermal method was employed to prepare the sodium niobate (NaNbO3) nanocubes. We executed time dependent experiments to illustrate the formation mechanism of sodium niobate nanocubes. It was observed that the morphology of NaNbO3 nanocubes was dependent on the reaction time and 12hr reaction time was found to be suitable. Morphology, composition, structure and optical properties of sodium niobate nanocubes were evaluated by scanning electron microscope, X-ray energy-dispersive spectrometer, X-ray diffraction and UV-visible diffuse reflectance spectrometer. The photocatalytic activity of sodium niobate was studied for photocatalytic hydrogen production. It was anticipated that the sodium niobate (NaNbO3) cubes exhibited good photocatalytic activity under UV light irradiation using lactic acid as sacrificial agent. The cytotoxicity activity of sodium niobate nanocubes was studied as well at different concentrations (5 mg/mL, 3 mg/mL, 1 mg/mL, and 0.25 mg/mL) against human colon colorectal carcinoma cell line (HCT116) by MTT assay and EC50 was found to be 1.9 mg/mL. Sodium niobate proved to be a good DPPH free radical scavenging material, tested at different concentrations. It was noticed that peak intensity at 517 nm was decreased after 30 minute incubation, further supporting the antioxidant activity. This study will be useful for design and engineering of materials that can be used in biomedical applications and in photocatalysis.

Extracts of Clove (Syzygium aromaticum) Potentiate FMSP-Nanoparticles Induced Cell Death in MCF-7 Cells.

Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do not elicit a significant response on cancer cells when treated alone. In the present study, we have tested fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude clove extracts on human breast cancer cells (MCF-7) to examine whether the combination approach enhance the cancer cell death. The MCF-7 cells were treated with different concentrations (1.25 µg/mL, 12.5 µg/mL, 50 µg/mL, 75 µg/mL, and 100 µg/mL) of FMSP-nanoparticles alone and in combination with 50 µg/mL crude clove extracts. The effects of FMSP-nanoparticles alone and combined with clove extracts were observed after 24 hrs and 48 hrs intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4',6-diamidino-2-phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. We have demonstrated that cancer cell viability was decreased to 55.40% when treated with FMSP-nanoparticles alone, whereas when cancer cells were treated with FMSP-nanoparticles along with crude clove extracts, the cell viability was drastically decreased to 8.50%. Both morphological and quantitative data suggest that the combination of FMSP-nanoparticles plus crude clove extracts are more effective in treating cancer cells and we suggest that the combination treatment of nanoparticles along with clove extracts hold a great promise for the cancer treatments.

Fluorescent magnetic submicronic polymer (FMSP) nanoparticles induce cell death in human colorectal carcinoma cells.

Nanoparticles have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. The aim of the present study is to examine whether fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) have any impact on human colorectal cancer cells. In the present study, we have tested FMSP-nanoparticles with an average size of 100-200 nm on human colorectal carcinoma cells (HCT-116) to check their cytotoxic and anti-cancer capabilities. The effects of FMSP-nanoparticles on cancer cells were observed after 6 h, 24 h and 48 h intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4lue-diamidino-2-phenylindole (DAPI) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Our MTT analysis results revealed that FMSP-nanoparticles produced dose-dependent effects on cancer cells, FMSP-nanoparticles with dose of 1.25 µg/mL did not decrease cell survivability, whereas dosages of 12.5 µg/mL and 50 µg/mL respectively showed 23.59% and 59.47% decrease in the cancer cell survivability. In conclusion, our results demonstrate FMSP-nanoparticles have a potential anti-cancer capability and hold a great promise for colon cancer treatments.

FMSP-Nanoparticles Induced Cell Death on Human Breast Adenocarcinoma Cell Line (MCF-7 Cells): Morphometric Analysis.

Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to the patients and cause unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we tested the effect of FMSP-nanoparticles on human breast cancer cells (MCF-7). We tested different concentrations (1.25, 12.5 and 50 µg/mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, a dose of 1.25 µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5 and 50 µg/mL resulted in significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate that FMSP-nanoparticles induce cell death in MCF-7 cells and may be a potential anti-cancer agent for breast cancer treatment.

Impact of nanoparticles on neuron biology: current research trends.

Nanoparticles have enormous applications in textiles, cosmetics, electronics, and pharmaceuticals. But due to their exceptional physical and chemical properties, particularly antimicrobial, anticancer, antibacterial, anti-inflammatory properties, nanoparticles have many potential applications in diagnosis as well as in the treatment of various diseases. Over the past few years, nanoparticles have been extensively used to investigate their response on the neuronal cells. These nanoparticles cause stem cells to differentiate into neuronal cells and promote neuronal cell survivability and neuronal cell growth and expansion. The nanoparticles have been tested both in in vitro and in vivo models. The nanoparticles with various shapes, sizes, and chemical compositions mostly produced stimulatory effects on neuronal cells, but there are few that can cause inhibitory effects on the neuronal cells. In this review, we discuss stimulatory and inhibitory effects of various nanoparticles on the neuronal cells. The aim of this review was to summarize different effects of nanoparticles on the neuronal cells and try to understand the differential response of various nanoparticles. This review provides a bird's eye view approach on the effects of various nanoparticles on neuronal differentiation, neuronal survivability, neuronal growth, neuronal cell adhesion, and functional and behavioral recovery. Finally, this review helps the researchers to understand the different roles of nanoparticles (stimulatory and inhibitory) in neuronal cells to develop effective therapeutic and diagnostic strategies for neurodegenerative diseases.

GANP interacts with APOBEC3G and facilitates its encapsidation into the virions to reduce HIV-1 infectivity.

The ssDNA-dependent deoxycytidine deaminase apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (A3G) is a potent restrictive factor against HIV-1 virus lacking viral-encoded infectivity factor (Vif) in CD4(+) T cells. A3G antiretroviral activity requires its encapsulation into HIV-1 virions. In this study, we show that germinal center-associated nuclear protein (GANP) is induced in activated CD4(+) T cells and physically interacts with A3G. Overexpression of GANP augments the A3G encapsidation into the virion-like particles and ΔVif HIV-1 virions. GANP is encapsidated in HIV-1 virion and modulates A3G packaging into the cores together with cellular RNAs, including 7SL RNA, and with unspliced HIV-1 genomic RNA. GANP upregulation leads to a significant increase in A3G-catalyzed G→A hypermutation in the viral genome and suppression of HIV-1 infectivity in a single-round viral infection assay. Conversely, GANP knockdown caused a marked increase in HIV-1 infectivity in a multiple-round infection assay. The data suggest that GANP is a cellular factor that facilitates A3G encapsidation into HIV-1 virions to inhibit viral infectivity.