After the initiation of the current outbreak, humans’ lives have been profoundly impacted by COVID-19. During the first months, no rapid and reliable detecting tool was readily available to sufficiently respond to the requirement of massive testing. In this situation, when the development of an effective vaccine requires at least a few months, it is crucial to be prepared by developing and commercializing affordable, accurate, rapid and adaptable biosensors not only to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) but also to be armed to avoid the pandemic in the earliest stages in the future. The COVID-19 diagnostic tools are categorized into two main groups of Nucleic Acid (NA)-based and protein-based tests. To date, nucleic acid-based detection has been announced as the gold-standard strategy for coronavirus detection; however, protein-based tests are promising alternatives for rapid and large-scale screening of susceptible groups. In this review, we discuss the current protein-based biosensing tools, the research advances and the potential protein-detecting strategies for COVID-19 detection. This narrative review aims to highlight the importance of the diagnostic tests, encourage the academic research groups and the companies to eliminate the shortcomings of the current techniques and step forward to mass-producing reliable point-of-care (POC) and point-of-need (PON) adaptable diagnostic tools for large-scale screening in the future outbreaks.

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused respiratory infection, resulting in more than two million deaths globally and hospitalizing thousands of people by March 2021. A considerable percentage of the SARS-CoV-2 positive patients are asymptomatic or pre-symptomatic carriers, facilitating the viral spread in the community by their social activities. Hence, it is critical to have access to commercialized diagnostic tests to detect the infection in the earliest stages, monitor the disease, and follow up the patients. Various technologies have been proposed to develop more promising assays and move toward the mass production of fast, reliable, cost-effective, and portable PoC diagnostic tests for COVID-19 detection. Not only COVID-19 but also many other pathogens will be able to spread and attach to human bodies in the future. These technologies enable the fast identification of high-risk individuals during future hazards to support the public in such outbreaks. This paper provides a comprehensive review of current technologies, the progress in the development of molecular diagnostic tests, and the potential strategies to facilitate innovative developments in unprecedented pandemics.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, this fatal disease has been the leading cause of the death of more than 3.9 million people around the world. This tragedy taught us that we should be well-prepared to control the spread of such infectious diseases and prevent future hazards. As a consequence, this pandemic has drawn the attention of many researchers to the development of portable platforms with short hands-on and turnaround time suitable for batch production in urgent pandemic situations such as that of COVID-19. Two main groups of diagnostic assays have been reported for the detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) including nucleic acid-based and protein-based assays. The main focus of this paper is on the latter, which requires a shorter time duration, less skilled technicians, and faces lower contamination. Furthermore, this paper gives an overview of the complementary metal-oxide-semiconductor (CMOS) biosensors, which are potentially useful for implementing point-of-care (PoC) platforms based on such assays. CMOS technology, as a predominant technology for the fabrication of integrated circuits, is a promising candidate for the development of PoC devices by offering the advantages of reliability, accessibility, scalability, low power consumption, and distinct cost.

Background: Phenylketonuria is an inborn metabolic disorder inherited in an autosomal recessive pattern. The detection of pathogenic variations improves the power of at-risk carrier and prenatal detection. We previously found Q375R a novel phenylalanine hydroxylase variation in phenylketonuria patients from the southwest of Iran. Objectives: Here, we aimed to evaluate the rate of the pathogenicity of this novel variant and three other intron variants (IVS9 + 32insA, IVS11 + 163delC, and IVS12 + 30C>T). Methods: The pathogenicity and some structural features of Q375R were analyzed using bioinformatics tools including SIFT, PolyPhen, Mutpred, MutationTaster, nSSNP Analyzer, SNP effect, 3DLigandSite, GeneSplicer, Human Splicing Finder, MaxEntScan, and FSPLICE. Results: According to the SIFT, PolyPhen, Mutpred, and MutationTaster reports, Q375R could be disease-causing. SNAP predicted Q375R as an intermediate damaging variation and nSSNP Analyzer predicted this variation to be neutral. I-Mutant3.0, FoldX, and Mustab showed a decrease in phenylalanine hydroxylase stability upon Q375R alteration. Conclusions: 3DLigandSite predicted that phenylalanine hydroxylase binding sites vary in mutant and wild-type proteins. Q375R could be considered an effective factor in the structure and function of phenylalanine hydroxylase. This may be useful in clinical detection of phenylketonuria in Iranian patients and their at-risk relatives. However, we need to do complementary in vitro and in vivo functional assessments for the evaluation and validation of the effects of this variation on phenylalanine hydroxylase function and structure.

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