The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is considered the greatest challenge to the global health community of the century as it continues to expand. This has prompted immediate urgency to discover promising drug targets for the treatment of COVID-19. The SARS-CoV-2 viral proteases, 3-chymotrypsin-like protease (3CLpro) and papain-like cysteine protease (PLpro), have become the promising target to study due to their essential functions in spreading the virus by RNA transcription, translation, protein synthesis, processing and modification, virus replication, and infection of the host. As such, understanding of the structure and function of these two proteases is unavoidable as platforms for the development of inhibitors targeting this protein which further arrest the infection and spread of the virus. While the abundance of reports on the screening of natural compounds such as SARS-CoV-2 proteases inhibitors are available, the microorganisms-based compounds (peptides and non-peptides) remain less studied. Indeed, microorganisms-based compounds are also one of the potent antiviral candidates against COVID-19. Microbes, especially bacteria and fungi, are other resources to produce new drugs as well as nucleosides, nucleotides, and nucleic acids. Thus, we have compiled various reported literature in detail on the structures, functions of the SARS-CoV-2 proteases, and potential inhibitors from microbial sources as assistance to other researchers working with COVID-19. The compounds are also compared to HIV protease inhibitors which suggested the microorganisms-based compounds are advantageous as SARS-CoV2 proteases inhibitors. The information should serve as a platform for further development of COVID-19 drug design strategies.

Cellulases are key enzymes in the enzymatic conversion of lignocellulose into fermentable sugars, with broad applications in bioenergy, feed processing, textiles, and sustainable waste management. This study aimed to characterize the cellulolytic activity of extracellular fractions from Bacillus amyloliquefaciens SLBD, a strain recently isolated from horse feces, while examining the effects of pH, temperature, and selected metal ions on enzyme activity, and to fractionate its extracellular proteins by size-exclusion chromatography (SEC) to identify and evaluate distinct cellulase fractions. Crude extracellular enzymes were produced through submerged fermentation and subsequently fractionated using SEC to obtain molecular-weight-based protein fractions. Cellulolytic activity was evaluated using carboxymethyl cellulose as substrate, and enzyme performance was assessed under various pH values, temperature ranges, and metal ion conditions. The results demonstrated that the extracellular cellulases exhibited optimal activity at moderate temperatures and maintained activity across a broad pH range, indicating favorable stability characteristics. Among the SEC fractions obtained, the smallest molecular-weight fraction displayed remarkably enhanced CMCase activity, exceeding that of the crude extract by more than 270-fold. SDS-PAGE analysis confirmed distinct protein profiles among fractions, supporting the effectiveness of SEC in activity-guided fractionation. Several metal ions, particularly Ca²⁺ and Zn²⁺, significantly stimulated enzymatic activity, while others exhibited inhibitory effects. These findings highlight the presence of low-molecular-weight, highly active extracellular cellulases produced by B. amyloliquefaciens SLBD. Overall, this study provided important insights into the functional diversity of bacterial cellulases and demonstrates the potential of SEC-based fractionation as an effective preliminary approach for identifying high-performance enzyme fractions.