Cyanobacteria are promising microorganisms for sustainable biotechnologies, yet unlocking their potential requires radical re-engineering and application of cutting-edge synthetic biology techniques. In recent years, the available devices and strategies for modifying cyanobacteria have been increasing, including advances in the design of genetic promoters, ribosome binding sites, riboswitches, reporter proteins, modular vector systems, and markerless selection systems. Because of these new toolkits, cyanobacteria have been successfully engineered to express heterologous pathways for the production of a wide variety of valuable compounds. Cyanobacterial strains with the potential to be used in real-world applications will require the refinement of genetic circuits used to express the heterologous pathways and development of accurate models that predict how these pathways can be best integrated into the larger cellular metabolic network. Herein, we review advances that have been made to translate synthetic biology tools into cyanobacterial model organisms and summarize experimental and in silico strategies that have been employed to increase their bioproduction potential. Despite the advances in synthetic biology and metabolic engineering during the last years, it is clear that still further improvements are required if cyanobacteria are to be competitive with heterotrophic microorganisms for the bioproduction of added-value compounds.

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Background The COVID-19 pandemic caused by SARS-CoV-2 has shown an exponential trend of infected people across the planet. Crediting its virulent nature, it becomes imperative to identify potential therapeutic agents against the deadly virus. The 3-chymotrypsin-like protease (3CLpro) is a cysteine protease which causes the proteolysis of the replicase polyproteins to generate functional proteins, which is a crucial step for viral replication and infection. Computational methods have been applied in recent studies to identify promising inhibitors against 3CLpro to inhibit the viral activity. Main body of the abstract This review provides an overview of promising drug/lead candidates identified so far against 3CLpro through various in silico approaches such as structure-based virtual screening (SBVS), ligand-based virtual screening (LBVS) and drug-repurposing/drug-reprofiling/drug-retasking. Further, the drugs have been classified according to their chemical structures or biological activity into flavonoids, peptides, terpenes, quinolines, nucleoside and nucleotide analogues, protease inhibitors, phenalene and antibiotic derivatives. These are then individually discussed based on the various structural parameters namely estimated free energy of binding (ΔG), key interacting residues, types of intermolecular interactions and structural stability of 3CLpro-ligand complexes obtained from the results of molecular dynamics (MD) simulations. Conclusion The review provides comprehensive information of potential inhibitors identified through several computational methods thus far against 3CLpro from SARS-CoV-2 and provides a better understanding of their interaction patterns and dynamic states of free and ligand-bound 3CLpro structures.

Phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) governs stage-specific interactions with different cellular machines. The CTD consists of Y 1 S 2 P 3 T 4 S 5 P 6 S 7 heptad repeats, and sequential phosphorylations of Ser7, Ser5 and Ser2 occur universally across Pol II-transcribed genes. Phosphorylation of Thr4, however, appears to selectively modulate transcription of specific classes of genes. Here, we identify 10 new Thr4 kinases from different kinase structural groups. Irreversible chemical inhibition of the most active Thr4 kinase, Hrr25, reveals a novel role for this kinase in transcription termination of specific class of noncoding snoRNA genes. Genome-wide profiles of Hrr25 reveal a selective enrichment at 3ʹ regions of noncoding genes that display termination defects. Importantly, phospho-Thr4 marks placed by Hrr25 are recognized by Rtt103, a key component of the termination machinery. Our results suggest that these uncommon CTD kinases selectively place phospho-Thr4 marks to regulate expression of targeted genes.

The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has resulted in almost 28 million cases of COVID-19 (Corona virus disease-2019) and more than 900000 deaths worldwide since December 2019. In the absence of effective antiviral therapy and vaccine, treatment of COVID-19 is largely symptomatic. By making use of its spike (S) protein, the virus binds to its primary human cell receptor, angiotensin converting enzyme 2 (ACE2) which is present in the pulmonary epithelial cells as well as other organs. SARS-CoV-2 may cause a downregulation of ACE2. ACE2 plays a protective role in the pulmonary system through its Mas-receptor and alamandine-MrgD-TGR7 pathways. Loss of this protective effect could be a major component of COVID-19 pathogenesis. An attractive strategy in SARS-CoV-2 therapeutics would be to augment ACE2 either directly by supplementation or indirectly through drugs which increase its levels or stimulate its downstream players. In this semi-systematic review, we have analysed the pathophysiological interplay between ACE and ACE2 in the cardiopulmonary system, the modulation of these two proteins by SARS-CoV-2, and potential therapeutic avenues targeting ACE-Ang II and ACE2-Ang (1–7) axes, that can be utilized against COVID-19 disease progression.