The global outbreak of COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome caused by Coronavirus 2) began in December 2019. Its closest relative, SARS-CoV-1, has a slightly mutated Spike (S) protein, which interacts with ACE2 receptor in human cells to start the infection. So far, there are no vaccines or drugs to treat COVID-19. So, research groups worldwide are seeking new molecules targeting the S protein to prevent infection by SARS-CoV-2 and COVID-19 establishment. We performed molecular docking analysis of eight synthetic peptides against SARS-CoV-2 S protein. All interacted with the protein, but Mo-CBP 3-PepII and PepKAA had the highest affinity with it. By binding to the S protein, both peptides led to conformational alterations in the protein, resulting in incorrect interaction with ACE2. Therefore, given the importance of the S protein-ACE2 interaction for SARS-CoV-2 infection, synthetic peptides could block SARS-CoV-2 infection. Moreover, unlike other antiviral drugs, peptides have no toxicity to human cells. Thus, these peptides are potential molecules to be tested against SARS-CoV-2 and to develop new drugs to treat COVID-19.
Three coronaviruses (CoVs) have threatened the world population by causing outbreaks in the last two decades. In late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged and caused the coronaviruses to disease 2019 (COVID-19), leading to the ongoing global outbreak. The other pandemic coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV), share a considerable level of similarities at genomic and protein levels. However, the differences between them lead to distinct behaviors. These differences result from the accumulation of mutations in the sequence and structure of spike (S) glycoprotein, which plays an essential role in coronavirus infection, pathogenicity, transmission, and evolution. In this review, we brought together many studies narrating a sequence of events and highlighting the differences among S proteins from SARS-CoV, MERS-CoV, and SARS-CoV-2. It was performed here, analysis of S protein sequences and structures from the three pandemic coronaviruses pointing out the mutations among them and what they come through. Additionally, we investigated the receptor-binding domain (RBD) from all S proteins explaining the mutation and biological importance of all of them. Finally, we discuss the mutation in the S protein from several new isolates of SARS-CoV-2, reporting their difference and importance. This review brings into detail how the variations in S protein that make SARS-CoV-2 more aggressive than its relatives coronaviruses and other differences between coronaviruses.
Latex fractions from Calotropis procera, Cryptostegia grandiflora, Plumeria rubra, and Himatanthus drasticus were assayed in order to prospect for new plant peptidases with milk-clotting activities, for use as rennet alternatives. Only C. procera and C. grandiflora latex fractions exhibited proteolytic and milk-clotting activities, which were not affected by high concentrations of NaCl and CaCl. However, pre-incubation of both samples at 75°C for 10min eliminated completely their activities. Both proteolytic fractions were able to hydrolyze k-casein and to produce peptides of 16kDa, a similar SDS-PAGE profile to commercial chymosin. RP-HPLC and mass spectrometry analyses of the k-casein peptides showed that the peptidases from C. procera or C. grandiflora hydrolyzed k-casein similar to commercial chymosin. The cheeses made with both latex peptidases exhibited yields, dry masses, and soluble proteins similar to cheeses prepared with commercial chymosin. In conclusion, C. procera and C. grandiflora latex peptidases with the ability to coagulate milk can be used as alternatives to commercial animal chymosin in the cheese manufacturing process.
C. albicans and C. parapsilosis are biofilm-forming yeasts responsible for bloodstream infections that can cause death. Synthetic antimicrobial peptides (SAMPs) are considered to be new weapons to combat these infections, alone or combined with drugs. Here, two SAMPs, called Mo-CBP3-PepI and Mo-CBP3-PepIII, were tested alone or combined with nystatin (NYS) and itraconazole (ITR) against C. albicans and C. parapsilosis biofilms. Furthermore, the mechanism of antibiofilm activity was evaluated by fluorescence and scanning electron microscopies. When combined with SAMPs, the results revealed a 2- to 4-fold improvement of NYS and ITR antibiofilm activity. Microscopic analyses showed cell membrane and wall damage and ROS overproduction, which caused leakage of internal content and cell death. Taken together, these results suggest the potential of Mo-CBP3-PepI and Mo-CBP3-PepIII as new drugs and adjuvants to increase the activity of conventional drugs for the treatment of clinical infections caused by C. albicans and C. parapsilosis.
The recent outbreak caused by SARS-CoV-2 continues to threat and take many lives all over the world. The lack of an efficient pharmacological treatments are serious problems to be faced by scientists and medical staffs worldwide. In this work, an
in silico
approach based on the combination of molecular docking, dynamics simulations, and quantum biochemistry revealed that the synthetic peptides
RcAlb
-PepI, PepGAT, and PepKAA, strongly interact with the main protease (Mpro) a pivotal protein for SARS-CoV-2 replication. Although not binding to the proteolytic site of SARS-CoV-2 Mpro,
RcAlb
-PepI, PepGAT, and PepKAA interact with other protein domain and allosterically altered the protease topology. Indeed, such peptide-SARS-CoV-2 Mpro complexes provoked dramatic alterations in the three-dimensional structure of Mpro leading to area and volume shrinkage of the proteolytic site, which could affect the protease activity and thus the virus replication. Based on these findings, it is suggested that
RcAlb
-PepI, PepGAT, and PepKAA could interfere with SARS-CoV-2 Mpro role
in vivo
. Also, unlike other antiviral drugs, these peptides have no toxicity to human cells. This pioneering
in
silico investigation opens up opportunity for further
in vivo
research on these peptides, towards discovering new drugs and entirely new perspectives to treat COVID-19.
Communicated by Ramaswamy H. Sarma
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