The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment. Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection. Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes. This process led to the selection of 9 compounds with optimal binding affinities to the target sites. The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78. However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78. Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78.
Trichosporonasahii is a basidiomycete yeast responsible for white piedra and onychomycosis in the immunocompetent host. In the immunocompromised patients, invasive infections are reported; their diagnosis is difficult and they are associated with high mortality rate. Urinary infection due to Trichosporon Asahi is rare but its incidenceis increasing. We report the case of a 58 year old diabetic patient. The yeast was isolated from urine samples of three consecutive crops in pure form. The patient improved after antifungal therapy.
The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than 502,539 deaths worldwide as of June 2020. The explosive spread of the virus and the rapid increase in the number of cases require the immediate development of effective therapies and vaccines as well as accurate diagnosis tools. The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of the ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the entry of the virus into host cells. In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS-CoV-2 to ACE2. First, the RBD-ACE2 interface in the 6M0J structure was studied by the MM-GBSA decomposition module of the HawkDock server, which led to the identification of two critical target regions in the RBD. Next, two virtual screening experiments of 7236 α-helix mimetics from ASINEX were conducted on the above regions using the iDock tool, which resulted in 10 candidates with favorable binding affinities. Finally, the stability of RBD complexes with the top-two ranked compounds was further validated by 40 ns MD simulations using Desmond package of Schrodinger.
Few data are published from Morocco on fungal disease, although numerous case reports attest to a wide range of conditions in the country. Here, we estimate for the first time the incidence and prevalence of serious fungal diseases in the country. Detailed literature searches in English and French were conducted for all serious fungal infections. Demographic and individual underlying condition prevalence or annual incidence were obtained from UNAIDS (HIV), WHO (TB) and other international sources. Deterministic modelling was then applied to estimate fungal disease burden. Morocco’s population in 2021 was 36,561,800. Multiple publications describe various fungal diseases, but epidemiological studies are rare. The most frequent serious fungal infections were tinea capitis (7258/100,000) and recurrent vulvovaginal candidiasis (2794/100,000 females). Chronic pulmonary aspergillosis is also common at a prevalence of 19,290 (53/100,000) because of the relatively high rate of tuberculosis. The prevalence of asthma in adults exceeds one million, of whom fungal asthma (including allergic bronchopulmonary aspergillosis (ABPA)) probably affects 42,150 (115/100,000). Data are scant on candidaemia (estimated at 5/100,000), invasive aspergillosis (estimated at 4.1/100,000), HIV-related complications such as cryptococcal meningitis and Pneumocystis pneumonia and mucormycosis. Fungal keratitis is estimated at 14/100,000). Mycetoma and chromoblastomycosis are probably rare. Fungal disease is probably common in Morocco and diagnostic capacity is good in the teaching hospitals. These estimates need confirmation with methodologically robust epidemiological studies.
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