A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (∼82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (M pro ) or 3-chymotrypsin-like cysteine protease (3CL pro ), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, M pro is highly conserved among various CoVs, and a mutation in M pro is often lethal to the virus. Thus, drugs targeting the M pro enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV M pro represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and Nterminal deletion of residues of SARS-CoV M pro on its dimerization and, thus, catalytic activity. We believe that the present review will stimulate research in this less explored yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The worldwide effort to develop peptide-based inhibitors of amyloid-β (Aβ) aggregation can be considered an unplanned combinatorial experiment. An understanding of what has been done and achieved may advance our understanding of AD pathology and the discovery of effective therapeutic agents. We review here the history of such peptide-based inhibitors, including those based on the Aβ sequence and those not derived from that sequence, containing both natural and unnatural amino acid building blocks. Peptide-based aggregation inhibitors hold significant promise for future AD therapy owing to their high selectivity, effectiveness, low toxicity, good tolerance, low accumulation in tissues, high chemical and biological diversity, possibility of rational design, and highly developed methods for analyzing their mode of action, proteolytic stability (modified peptides), and blood-brain barrier (BBB) permeability.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The Food and Drug Administration has approved drugs (e.g., rivastigmine, donepezil, galantamine, and memantine) that at best provide marginal benefits, thus emphasizing the urgent need to explore other molecular entities as future drug candidates for AD. Looking at the wide pharmaceutical applications of heterocyclic compounds and particularly those containing benzofuran and indole ring systems, these molecular frameworks have drawn special attention from medicinal chemists for further evaluation in numerous diseases. This article focuses on the history and recent advances of benzofuran- and indole-based compounds as inhibitors of butyrylcholinesterase, acetylcholinesterase, γ-secretase, β-secretase, tau misfolding, and β-amyloid aggregation.

Using 1,3-dithian-2-yl-methoxycarbonyl (Dmoc) as protecting groups and linker for oligodeoxynucleotide (ODN) synthesis, deprotection and cleavage are achieved under non-nucleophilic oxidative conditions. The nucleophile-sensitive thioester and α-chloroacetyl groups are conveniently incorporated into ODN sequences. The technology could be universally useful for electrophilic ODN synthesis.

Here we describe several useful strategies to a variety of unusual α-amino acid derivatives and peptides based on "building block" approach. These building blocks are suitable for modification at an amino acid as well as at a peptide level. Moreover, these methods have embedded several points for diversification and are capable of producing a library of modified amino acids and peptides. We have employed highly atom-economic processes such as the Diels-Alder reaction, [2 + 2 + 2] cycloaddition, Suzuki-Miyaura cross-coupling, and olefin metathesis as key steps to assemble various unnatural amino acid derivatives and peptides. In some instances, we have used rongalite to generate Diels-Alder precursors.

We describe diverse approaches to various dienes and their utilization in the Diels-Alder reaction to produce a variety of polycycles. The dienes covered here are prepared by simple alkylation reaction or via the Claisen rearrangement or by enyne metathesis of alkyne or enyne building blocks. Here, we have also included the Diels-Alder chemistry of dendralenes, a higher analog of cross-conjugated dienes. The present article is inclusive of o-xylylene derivatives that are generated in situ starting with benzosultine or benzosulfone derivatives. The Diels-Alder reaction of these dienes with various dienophiles gave diverse polycyclic systems and biologically important targets.

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Type 2 diabetes (T2D) is a chronic metabolic disease characterized by insulin resistance and a progressive loss of pancreatic islet β-cell mass, which leads to insufficient secretion of insulin and hyperglycemia. Emerging evidence suggests that toxic oligomers and fibrils of human islet amyloid polypeptide (hIAPP) contribute to the death of β-cells and lead to T2D pathogenesis. These observations have opened new avenues for the development of islet amyloid therapies for the treatment of T2D. The peptidebased inhibitors are of great value as therapeutic agents against hIAPP aggregation in T2D owing to their biocompatibility, feasibility of synthesis and modification, high specificity, low toxicity, proteolytic stability (modified peptides), and weak immunogenicity as well as the large size of involved interfaces during self-aggregation of hIAPP. An understanding of what has been done and achieved will provide key insights into T2D pathology and assist in the discovery of more potent drug candidates for the treatment of T2D. In this article, we review various peptide-based inhibitors of hIAPP aggregation, including those derived from the hIAPP sequence and those not based on the sequence, consisting of both natural as well as unnatural amino acids and their derivatives. The present review will be beneficial in advancing the field of peptide medicine for the treatment of T2D.