The status of teachers' collaboration in Ethiopian public universities found in the Amhara region.

Research findings on the issue of teachers' collaboration in Ethiopian higher education institutions are limited. The main objective of this study was to examine the status of teachers' collaboration in Ethiopian public universities found in the Amhara region. In addition, this study also aimed at comparing the status of teachers' collaboration among the four generations of Ethiopian public universities found in the Amhara Region. Using a convergent parallel mixed design, data were collected from teachers, department heads, and academic deans through questionnaires and interviews using a multistage stratified sampling procedure. Four universities were selected from the ten public universities after stratifying them into four categories based on generations. From the sampled universities, 250 participants were selected randomly to complete a self-administered questionnaire. In addition, 8 teachers, 4 department heads, and 4 academic deans were selected using the purposive sampling technique for the interview. The quantitative data collected through a close-ended questionnaire were analyzed using mean, standard deviation, t-test, and one-way ANOVA, and the qualitative data were analyzed using thematic analysis. Finally, the qualitative and quantitative results were blended to compare or relate to each other. The findings of this study revealed that university teachers found in the Amhara region were moderately collaborative in information sharing and informal collaborations/collegial relationships. However, teachers' collaboration in professional activities seems unsatisfactory. The result of this research also indicated that there is a significant difference across the four generations of universities. Hence, Ethiopian public universities found in the Amhara region should give adequate attention to strengthening collaboration among teachers in professional activities.

Academic collaboration in Ethiopian Higher Education Institutions: from a senior-junior staff support perspective.

This study examined the level of collaboration between senior and junior academic staff in Higher Education Institutions in the Amhara Regional State, Ethiopia. We employed a convergent parallel mixed research design and collected data from 203 teachers, four department heads, and four academic deans using questionnaires and semi-structured interviews. The researchers also employed frequencies, percentages, mean, standard deviations, independent sample t-test, and one-way analysis on variance to analyze and interpret the quantitative data. The qualitative data on the other hand, was analyzed thematically using reflexive thematic analysis. The results show that the collaboration between senior and junior faculty members is too weak and limited to information exchange and material-sharing practices. The study also shows that independent variables such as gender and level of qualification did not affect senior and junior staff collaboration, while age and teaching experience affected it. We recommend the concerned bodies in higher education institutions to establish a system that entertains a genuine collaborative culture between senior and junior academic staff, following an integrative approach among different groups and considering all the challenges in realizing such an effective collaboration.

Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs.

In this report, a series of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives were designed to explore the hydrophobic channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating an aromatic moiety to the left wing of the lead K-5a2. The newly synthesized compounds were evaluated for anti-HIV potency in MT-4 cells and inhibitory activity to HIV-1 reverse transcriptase (RT). Most of the synthesized compounds exhibited broad-spectrum activity toward wild-type and a wide range of HIV-1 strains carrying single non-nucleoside reverse transcriptase inhibitors (NNRTI)-resistant mutations. Especially, compound 26 exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC50 ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR). Moreover, the RT inhibition activity, preliminary structure-activity relationship and molecular docking were also investigated. Furthermore, 26 exhibited favorable pharmacokinetics (PK) profiles and with a bioavailability of 33.8%. Taken together, the results could provide valuable insights for further optimization and compound 26 holds great promise as a potential drug candidate for the treatment of HIV-1 infection.

Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non-nucleoside hepatitis B virus inhibitors by exploring the solvent-exposed region.

In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have explored the solvent-exposed protein region of heteroaryldihydropyrimidine derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non-nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti-HBV DNA replication activity compared to lamivudine. In particular, compound II-1 displayed the most potent activity against HBV DNA replication (IC50  = 0.35 ± 0.04 µM). The preliminary structure-activity relationships of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design.

Design, synthesis and biological evaluation of "Multi-Site"-binding influenza virus neuraminidase inhibitors.

Encouraged by our earlier discovery of neuraminidase inhibitors targeting 150-cavity or 430-cavity, herein, to yield more potent inhibitors, we designed, synthesized, and biologically evaluated a series of novel oseltamivir derivatives via modification of C-1 and C5-NH2 of oseltamivir by exploiting 150-cavity and/or 430-cavity. Among the synthesized compounds, compound 15e, the most potent N1-selective inhibitor targeting 150-cavity, showed 1.5 and 1.8 times greater activity than oseltamivir carboxylate (OSC) against N1 (H5N1) and N1 (H5N1-H274Y). In cellular assays, 15e also exhibited greater potency than OSC against H5N1 with EC50 of 0.66 µM. In addition, 15e demonstrated low cytotoxicity in vitro and low acute toxicity in mice. Molecular docking studies provided insights into the high potency of 15e against N1 and N1-H274Y mutant NA. Overall, we envisioned that the significant breakthrough in the discovery of potent group-1-specific neuraminidase inhibitors may lead to further investigation of more potent anti-influenza agents.

The progress in the development of HIV inhibitors targeting protein-protein interactions / 药学学报

Protein-protein interaction (PPI) plays an important role in many steps of the human immunodeficiency virus (HIV) life cycle. Targeting these protein-protein interactions, especially the interaction between the virus with host cells, can provide new insights into the development of HIV inhibitors with novel mechanisms of action. Herein, we review the latest discoveries of PPI inhibitors based on the mechanisms of action of various protein-protein interactions with specific research examples.

Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of Group-1 and -2 Influenza A Neuraminidases, Including a Drug-Resistant Variant.

On the basis of our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Among the synthesized compounds, 15b and 15c were exceptionally active against both group-1 and -2 NAs. Especially for 09N1, N2, N6, and N9 subtypes, they showed 6.80-12.47 and 1.20-3.94 times greater activity than oseltamivir carboxylate (OSC). They also showed greater inhibitory activity than OSC toward H274Y and E119V variant. In cellular assays, they exhibited greater potency than OSC toward H5N1, H5N2, H5N6, and H5N8 viruses. 15b demonstrated high metabolic stability, low cytotoxicity in vitro, and low acute toxicity in mice. Computational modeling and molecular dynamics studies provided insights into the role of R group of 15b in improving potency toward group-1 and -2 NAs. We believe the successful exploitation of the 150-cavity of NAs represents an important breakthrough in the development of more potent anti-influenza agents.

Discovery of Novel Diarylpyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the "NNRTI Adjacent" Binding Site.

A novel series of diarylpyrimidine derivatives, which could simultaneously occupy the classical NNRTIs binding pocket (NNIBP) and the newly reported "NNRTI Adjacent" binding site, were designed, synthesized, and evaluated for their antiviral activities in MT-4 cell cultures. The results demonstrated that six compounds (20, 27 and 31-34) showed excellent activities against wild-type (WT) HIV-1 strain (EC50 = 2.4-3.8 nM), which were more potent than that of ETV (EC50 = 4.0 nM). Furthermore, 20, 27, 33, and 34 showed more potent or equipotent activity against single mutant HIV-1 strains compared to that of ETV. Especially, 20 showed marked antiviral activity, which was 1.5-fold greater against WT and 1.5- to 3-fold greater against L100I, K103N, Y181C, Y188L, and E138K when compared with ETV. In addition, all compounds showed lower toxicity (CC50 = 5.1-149.2 µM) than ETV (CC50 = 2.2 µM). The HIV-1 RT inhibitory assay was further conducted to confirm their binding target. Preliminary structure-activity relationships (SARs), molecular modeling, and calculated physicochemical properties of selected compounds were also discussed comprehensively.