TY  - JOUR
A1  - Zahran, Eman Maher
A1  - Albohy, Amgad
A1  - Khalil, Amira
A1  - Ibrahim, Alyaa Hatem
A1  - Ahmed, Heba Ali
A1  - El-Hossary, Ebaa M.
A1  - Bringmann, Gerhard
A1  - Abdelmohsen, Usama Ramadan
T1  - Bioactivity Potential of Marine Natural Products from Scleractinia-Associated Microbes and In Silico Anti-SARS-COV-2 Evaluation
JF  - Marine Drugs
N2  - Marine organisms and their associated microbes are rich in diverse chemical leads. With the development of marine biotechnology, a considerable number of research activities are focused on marine bacteria and fungi-derived bioactive compounds. Marine bacteria and fungi are ranked on the top of the hierarchy of all organisms, as they are responsible for producing a wide range of bioactive secondary metabolites with possible pharmaceutical applications. Thus, they have the potential to provide future drugs against challenging diseases, such as cancer, a range of viral diseases, malaria, and inflammation. This review aims at describing the literature on secondary metabolites that have been obtained from Scleractinian-associated organisms including bacteria, fungi, and zooxanthellae, with full coverage of the period from 1982 to 2020, as well as illustrating their biological activities and structure activity relationship (SAR). Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and 15 compounds were selected. The selected compounds were virtually investigated for potential inhibition for SARS-CoV-2 targets using molecular docking studies. Promising potential results against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented.
KW  - Scleractinia
KW  - marine bacteria
KW  - marine fungi
KW  - zooxanthellae
KW  - marine natural products
KW  - ADME analysis
KW  - SARS-CoV-2
KW  - molecular docking
KW  - RNA-dependent RNA polymerase
KW  - methyltransferase
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220041
SN  - 1660-3397
VL  - 18
IS  - 12
ER  - 
TY  - JOUR
A1  - Kokic, Goran
A1  - Hillen, Hauke S.
A1  - Tegunov, Dimitry
A1  - Dienermann, Christian
A1  - Seitz, Florian
A1  - Schmitzova, Jana
A1  - Farnung, Lucas
A1  - Siewert, Aaron
A1  - Höbartner, Claudia
A1  - Cramer, Patrick
T1  - Mechanism of SARS-CoV-2 polymerase stalling by remdesivir
JF  - Nature Communications
N2  - Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryoelectron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication.
KW  - SARS-CoV-2 polymerase
KW  - Remdesivir
KW  - RNA-dependent RNA polymerase
KW  - Molecular mechanism
KW  - Biochemistry
KW  - Cryoelectron microscopy
KW  - RNA
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220979
VL  - 12
ER  -