Astract. SARS-CoV-2 is the virus that causes the COVID-19 disease, responsible for the second pandemic of the 21st century. This virus has caused a health emergency due to its rapid transmission and high mortality rate. The use of disinfectants of chemical origin has increased considerably to avoid contamination by SARS-CoV-2 but when used incorrectly they can pose a health risk. Citrus-based extracts have shown effectiveness in controlling the development of fungi and bacteria in in vitro and in situ studies. In in vitro cell assays, citrus extracts are effective in controlling the replication of disease-causing viruses. The objective of this review is to describe the problem of COVID-19, its transmission mechanisms, the use of chemical disinfectants and citrus extracts to control microorganisms and its suggested use as a complement in COVID-19 prevention. The use of citrus extracts has certain advantages such as biodegradability and low health risks. Thus, they could be a viable alternative to be used as a complement in the management and prevention of the spread of SARS-CoV-2.

Key words: SARS-CoV-2, disinfectant, COVID-19

SARS-CoV-2 Prevention

SARS-CoV-2 is an emerging coronavirus that causes the COVID-19 disease, the clinical manifestation of which can include a wide spectrum of non-specific symptoms such as severe acute respiratory syndrome (SARS), which can be fatal. This virus is responsible for the second pandemic of the 21st century, which has caused millions of deaths throughout the world (Scholten et al., 2020; Valero-Cedeño et al., 2020). As a result of the health emergency caused by the pandemic, the use of chemical disinfectants has increased to avoid infection with SARS-CoV-2. However, their excessive and incorrect use can pose various health risks that can manifest in complications such as toxicological and allergic conditions (Neto et al., 2020; Romero, 2013). Alternatives of natural origin, such as citrus extracts, have been evaluated as a means to prevent contamination by microorganisms (fungi and bacteria). Some studies have focused on the effectiveness of these extracts to control virus replication in human cells (Balesterieri et al., 2011; Olvera and Quiroz, 2018). The present study makes a general description of the transmission mechanisms of SARS-CoV-2, the effectiveness of chemical disinfectants and citrus extracts to inhibit microorganisms, and their potential as a complement in preventing COVID-19.

SARS-CoV-2 and transmission mechanisms

Coronaviruses (CoV) are a family of viruses that can infect both animals and humans, causing different complications, from a common cold to serious diseases such as SARS (Valero-Cedeño et al., 2020; Pérez et al., 2020). This virus family is classified into four genera (alpha, beta, gamma, and delta). The first two cause respiratory diseases in humans. Coronaviruses have a lipid membrane encircling the protein capsid, from which protein spicules (S protein) protrude. These spicules play an essential role in the infection of host cells. The genome of these viruses is a single-stranded RNA molecule of positive polarity that codes for several proteins that control the infected cell to produce a large quantity of new viral particles (H. García-Ruiz et al. In this Special Issue) (Huang et al., 2020). COVID-19 is caused by a beta coronavirus of zoonotic origin (Scholten et al., 2020), which means that humans are highly susceptible to infection with this virus due to their lack of immunological factors. This virus is currently responsible for a global health emergency due to its ability for rapid geographic spread through infected individuals, effective community transmission depending on the virus variant, high mortality and morbidity rates, and the lack of effective specific clinical treatments (Valero et al., 2020; Plasencia-Urizarri et al., 2020). At press time, the World Health Organization (WHO) recognizes five commercial vaccines against this virus that have been applied since December 2020 (Editor’s Note).

In short distances (≤1.5m), coronavirus contagion occurs through small droplets of respiratory secretions (>5 microns) that can be inhaled into the respiratory tract. These droplets are produced when coughing, talking, and sneezing. Contagion can also occur through direct contact between a healthy person and a sick person, or through contaminated surfaces when viral particles in the hands enter into the oral, respiratory, or ocular mucosa (WHO, 2021). Given these transmission mechanisms, the use of personal protective equipment and constant disinfection of contact surfaces are recommended to prevent the spread of this virus (Molina and Abad-Corpa, 2020). Transmission can occur through asymptomatic people during the incubation phase, through symptomatic people and people in recovery. The maximum release of infectious particles occurs during the symptomatic phase. Dispersion through food or water has not been demonstrated (Vargas-Arispuro et al. In this Special Issue). However, poor handling of food and water after possible contamination from sick people could spread the virus to people who consume them (Trilla, 2020; Pérez et al., 2020; Calvo et al., 2020; Deossa et al., 2020). SARS-CoV-2 particles have been shown to persist on copper (4 h), aluminum (2-8 h), stainless steel (48 h), latex and nitrile (<8 h), paper (more tan 72 h), cardboard (24 h), Wood (48 h), and for longer periods on iron (nine days) (Deossa et al., 2020; Álvarez et al., 2020; Kamps et al., 2020). The continuous disinfection of surfaces and hands is parto f the preventive management of COVID-19. Together with the use of protective equipment, the disinfection of surfaces is an efficient and economical alternative to deal with SARS-CoV-2 (Molina and Abad-Corpa, 2020).

Use of disinfectants in COVID-19 prevention

Disinfectants can eliminate microorganisms from surfaces and objects located in human hábitats, while the use of sanitizer reduces the amount of the inoculum below a safe level. In the case of SARS-CoV-2, disinfection has been the strategy adopted due to the lack of information about the pathogenic processes of the virus (https:// www.who.int/). A wide range of disinfectants has been used throughout the world to prevent contamination with SARS-CoV-2. The approval of each disinfectant depends on the requirements established by the local authority (WHO, 2020). The following chemical disinfectants are used intensively for COVID-19 prevention: sodium hypochlorite 0.1%, ethanol> 71%, ethyl alcohol> 70%, hydrogen peroxide 0.5%, benzalkonium chloride 0.05-0.2%, and chlorhexidine digluconate at 0.002% in liquid or gel presentations (Molina, 2020; Neto et al., 2020). However, the excessive or inappropriate use of these products has led to health problems. The US Center for Disease Control and Prevention reports a 20% increase in poisonings related to exposure to cleaning products and disinfectants compared to previous years. This has been attributed mainly to sustained and frequent exposure to chemical products and to the simultaneous use of more than one compound that when in contact, can release gases or highly toxic or allergenic compounds (Neto et al., 2020). Given the health risks posed by chemical products, alternatives of natural origin, safe for consumers and environmentally innocuous, have been developed. These natural alternatives also have a high capacity to inhibit or stop the growth of microorganisms. Citrus extracts are a commonly used natural disinfection alternative against various microorganisms due to their accessibility to the general population (Romero, 2013).

Citrus fruit extracts as disinfectants

Citrus fruits are rich in vitamin C, anthocyanins, and flavonones. The most abundant compounds in citrus fruits are hesperidin, naringin, limonene, and pectin. These compounds have been shown to have antioxidant, anti-inflammatory, antimicrobial, and antiviral activity. Citrus extracts are Generally Recognized as Safe (GRAS) compounds by the Food and Drug Administration (FDA) (Olvera and Quiroz, 2018; Yousaf et al., 2018; Narváez et al., 2017). The antimicrobial effectiveness of citrus extracts has been demonstrated in several studies (Table 1). De la Cruz et al. (2012) carried out a comparative study between the activity of chlorhexidine, a disinfectant for commercial use, and three disinfectants based on citrus and ethanol. The authors reported that the germicidal activity of the citrus extracts was effective, inhibiting 100% of the Colony Forming Units (CFU) of bacteria such as Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Similarly, Rodríguez (2014) reported the antimicrobial efficacy of a grapefruit seed extract on edible plant surfaces, where it reduced the microbial load (100-1400 CFU cm2 of mesophilic aerobes), while in the control there were countless strains. The antimicrobial activity of a disinfectant made from seeds and orange peel was evaluated against E. coli and S. aureus at two different contact times (5 and 10 min). The author reported a decrease in bacterial CFU after 10 minutes of exposure (Flores, 2017). There are few studies on the antiviral effect of citrus extracts used as a disinfectant on objects and surfaces; however, their effectiveness against viruses has been shown in in vitro cell studies. There are reports of the antiviral activity of citrus extracts against hepatitis, HIV, and respiratory viruses (RSV), as well as against viruses of the coronavirus family, including the SARS-CoV-2 virus (Table 2). Balestrieri et al. (2011) reported that the mechanism of action of citrus seed extracts includes the inactivation of viral particles. Recent studies have shown that grapefruit and orange extracts can inhibit 3CLpro, a SARS 2003 virus protease required for viral replication in in vitro cell assays (Bellavite and Donzelli, 2021). Similarly, extracts of sweet orange act against the replication of the murine coronavirus MHV-A59 (mouse hepatitis virus-A59), affecting the regulation of TRP genes, which are involved in the cellular antiviral response (Ulasli et al., 2014).

Citrus extracts as disinfectants in COVID-19 prevention

In response to the pandemic caused by the SARS-CoV-2 virus, governments around the world have promoted the disinfection of poorly ventilated or prolonged contact areas, such as transport units, using thermal foggers, which produce very fine droplets with a diameter between 1 and 50 mm, forming a uniformly distributed mist. Given the risks posed by chemical sanitizers and disinfectants, preference should be given to alternatives that are harmless to the environment and safe for humans. There is a high risk of contagion in public transport systems due to reduced spaces and poor ventilation. Surveys carried out by INEGI (2021) report that the subway system of Mexico City had an influx of more than 820 million passengers in 2020, without considering users of other public transport systems. These conditions are propitious for the spread of contagions. Thus, to reduce the risk of contagion by SARS-CoV-2 it is necessary to keep public transport and similar work and social spaces disinfected and sanitized. There are currently several commercial biodegradable products based on citrus extracts such as Biocitrox, Biocitric, and Citrocover, among others, that inhibit the development of fungi, bacteria, and viruses. In the face of the health emergency caused by SARS-CoV-2, these products can be an alternative to prevent contagious processes in community settings. In the states of Chihuahua and Jalisco, disinfection measures are carried out with Citrocover, applied using thermal foggers in public transport units in order to prevent contagion and curb the increase in positive cases of SARS-CoV-2 (Personal Communication, 2021. G.I. Sánchez Pacheco. 5VID Company. Cuauhtémoc, Chihuahua; Chihuahua Informa, 2020). Since COVID-19 could become a recurrent disease, a sustainable preventive strategy could allow the reactivation of socio-economic and cultural activities under safe conditions. Science has had to work quickly and effectively to find alternatives against COVID-19. However, it is necessary to encourage research on natural, safe, economical, and biodegradable alternatives that complement other strategies for the prevention and mitigation of the disease.

CONCLUSIONS

Citrus extracts are effective in controlling the growth of fungi and bacteria. So far, the use of extracts as disinfectants in public settings has not been widely studied. However, in vitro cell research indicates that citrus extracts are effective in inhibiting the replication of various viruses, including SARS-CoV-2. This suggests the potential of citrus extracts for the prevention and mitigation of COVID-19. Needless to say, this alternative must be based on scientific evidence to guarantee the efficient management and prevention of COVID-19.