ABSTRACT: The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease caused by Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) (Prec Clin Med 2020;3:9–13, Lancet 2020;395:497–506, N. Engl J Med 2020a;382:1199–207, Nature 2020;579:270–3). SARS-CoV-2 surveillance is essential to controlling widespread transmission. However, there are several challenges associated with the diagnostic of the COVID-19 during the current outbreak (Liu and Li (2019), Nature 2020;579:265–9, N. Engl J Med 2020;382:727–33). Firstly, the high number of cases overwhelms diagnostic test capacity and proposes the need for a rapid solution for sample processing (Science 2018;360:444–8). Secondly, SARS-CoV-2 is closely related to other important coronavirus species and subspecies, so detection assays can give false-positive results if they are not efficiently specific to SARS-CoV-2. Thirdly, patients with suspected SARS-CoV-2 infection sometimes have a different respiratory viral infection or co-infections with SARS-CoV-2 and other respiratory viruses (MedRxiv 2020a;1–18). Confirmation of the COVID-19 is performed mainly by virus isolation followed by RT-PCR and sequencing (N. Engl J Med 2020;382:727–33, MedRxiv 2020a, Turkish J Biol 2020;44:192–202). The emergence and outbreak of the novel coronavirus highlighted the urgent need for new therapeutic technologies that are fast, precise, stable, easy to manufacture, and target-specific for surveillance and treatment. Molecular biology tools that include gene-editing approaches such as CRISPR-Cas12/13-based SHERLOCK, DETECTR, CARVER and PAC-MAN, antisense oligonucleotides, antisense peptide nucleic acids, ribozymes, aptamers, and RNAi silencing approaches produced with cutting-edge scientific advances compared to conventional diagnostic or treatment methods could be vital in COVID-19 and other future outbreaks. Thus, in this review, we will discuss potent the molecular biology approaches that can revolutionize diagnostic of viral infections and therapies to fight COVID-19 in a highly specific, stable, and efficient way. Highlights SARS-CoV-2 is an RNA virus that could be targeted and diagnosed with novel CRISPR approaches. ASO therapy targeting transcript encoding a viral protein or genomic RNA itself could be developed as a response to the SARS-CoV-2 pandemic. Antisense peptide nucleic acids, which have significant potential as antiviral agents, are important therapeutic candidates that can target SARS-CoV-2 RNA with high hybridization affinity and stability. Although ribozyme and aptamer technologies are relatively older than other gene-editing technologies, they are still strong candidates in the fight against the COVID-19 pandemic due to their high specificities and low toxicities, besides that aptamers are highly reproducible. siRNAs that target structural or non-structural proteins of SARS-CoV-2, could inhibit assembly and replication of SARS-CoV-2.