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Short synthetic peptide molecules which bind to a specific target protein with a high affinity to exert its function are known as peptide aptamers. The high specificity of aptamers with small-molecule targets (metal ions, dyes and theophylline; ATP) is within 1 pM and 1 μM range, whereas with the proteins (thrombin, CD4 and antibodies) it is in the nanomolar range (which is equivalent to monoclonal antibodies). The recently identified coronavirus (SARS-CoV-2) genome encodes for various proteins, such as envelope, membrane, nucleocapsid, and spike protein. Among these, the protein necessary for the virus to enter inside the host cell is spike protein. The work focuses on designing peptide aptamer targeting the spike receptor-binding domain of SARS-CoV-2. The peptide aptamer has been designed by using bacterial Thioredoxin A as the scaffold protein and an 18-residue-long peptide. The tertiary structure of the peptide aptamer is modeled and docked to spike receptor-binding domain of SARS CoV2. Molecular dynamic simulation has been done to check the stability of the aptamer and receptor-binding domain complex. It was observed that the aptamer binds to spike receptor-binding domain of SARS-CoV-2 in a similar pattern as that of ACE2. The aptamer–receptor-binding domain complex was found to be stable in a 100 ns molecular dynamic simulation. The aptamer is also predicted to be non-antigenic, non-allergenic, non-hemolytic, non-inflammatory, water-soluble with high affinity toward ACE2 than serum albumin. Thus, peptide aptamer can be a novel approach for the therapeutic treatment for SARS-CoV-2. Graphical abstract

The newly identified SARS CoV2 has become a global pandemic since December 2019. Various researchers are trying to design a vaccine candidate against the virus. On the other hand, another group is focussing on repurposing approved or clinically tested drugs for treatment. However, there is always a search for alternative therapies. Thus, we propose an alternative approach apart from chemotherapy that is the usage of miRNA as novel antisense therapy to cure SARS CoV2 infected patients. To address the objective, miRNAs have been designed by targeting the genome of SARS CoV2 (Indian isolate). First, the open reading frames in the viral genome have been identified, and the proteins encoded by those open reading frames have been predicted. Using computational biology, several miRNAs have been designed and their probability to bind to a viral gene has been predicted. In addition, miRNA target mining in the host cell has been done to rule out the possibility of non-specific binding of the miRNAs. The miRNAs having the highest chances to bind to the viral genome have been converted into pre-miRNAs, and their interaction with dicer endoribonuclease has been studied by molecular docking. Results revealed that the pre-miRNAs interact with the RNAse III 2 domain of dicer. Thus, it is predicted that the pre-miRNAs after delivery to the infected host cell will be processed by dicer to generate mature miRNAs that will target the SARS CoV2 viral genome. Therefore, miRNA therapy can be an alternative approach for the treatment of SARS CoV2 infection.